Trial Outcomes & Findings for A Pilot Project Exploring the Impact of Whole Genome Sequencing in Healthcare (NCT NCT01736566)

Results Overview

Adapted measures (Hall, MA, et al. 2006) assessed participants' attitudes toward genetic information, trust of their physicians and the medical system regarding interpretation and use of genetic information. Higher scores on a 12-60 scale represent more positive attitudes and greater trust.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

213 participants

Primary outcome timeframe

Change at 6-weeks post-results disclosure relative to baseline, administered approx.12.5 months after baseline

Results posted on

2024-08-27

Participant Flow

Participant recruitment began in 2012 at Brigham and Women's hospital by letter, email, phone and in person.

Participant milestones

Participant milestones
Measure	Family History + Whole Genome Sequencing: Primary Care Doctors and their patients receive a Genome Report and an Annotated Family History Report. Main Study Experimental: Standard of Care + Whole Genome Sequencing (Genome Report): Doctors and their patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient.	Family History Only: Primary Care Doctors and their patients receive an Annotated Family History Report only. Active Comparator: Standard of Care Only: Doctors and their patients receive a Family History report only	Family History + Whole Genome Sequencing: Cardiology Doctors and their patients receive a Genome Report and an Annotated Family History Report. Main Study Experimental: Family History + Whole Genome Sequencing (Genome Report): Doctors and their patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient. Extension Phase: Experimental: Family History + Whole Genome Sequencing (Genome Report) \*In the main study participants are randomized between Experimental and Comparator, in the Extension phase of the study all participants are in the Experimental Arm.	Family History Only: Cardiology Doctors and their patients receive an Annotated Family History Report only. Active Comparator: Family History Only: Doctors and their patients receive a Family History report only	Extension Cohort Family History + Whole Genome Sequencing (Genome Report): Doctors and their African American patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient.
Main Study STARTED	51	50	50	52	10
Main Study COMPLETED	50	50	49	51	6
Main Study NOT COMPLETED	1	0	1	1	4
Long Term Follow-up STARTED	26	16	25	25	4
Long Term Follow-up COMPLETED	26	16	25	25	4
Long Term Follow-up NOT COMPLETED	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Pilot Project Exploring the Impact of Whole Genome Sequencing in Healthcare

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Family History + Whole Genome Sequencing: Primary Care n=51 Participants Doctors and their patients receive a Genome Report and an Annotated Family History Report. Main Study Experimental: Family History + Whole Genome Sequencing (Genome Report): Doctors and their patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient. Extension Phase: Experimental: Family History + Whole Genome Sequencing (Genome Report) \*In the main study participants are randomized between Experimental and Comparator, in the Extension phase of the study all participants are in the Experimental Arm.	Family History Only: Primary Care n=50 Participants Doctors and their patients receive an Annotated Family History Report only. Active Comparator: Standard of Care Only: Doctors and their patients receive a Family History report only	Family History + Whole Genome Sequencing - Cardiology n=50 Participants Doctors and their patients receive a Genome Report and an Annotated Family History Report. Main Study Experimental: Family History + Whole Genome Sequencing (Genome Report): Doctors and their patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient. Extension Phase: Experimental: Family History + Whole Genome Sequencing (Genome Report) \*In the main study participants are randomized between Experimental and Comparator, in the Extension phase of the study all participants are in the Experimental Arm.	Family History Only: Cardiology n=52 Participants Doctors and their patients receive an Annotated Family History Report only. Active Comparator: Family History Only: Doctors and their patients receive a Family History report only	Extension Cohort n=10 Participants Doctors and their patients receive a Genome Report and an Annotated Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient. * In the main study, participants are randomized between Experimental and Comparator. For the Extension cohort, all participants receive whole genome sequencing.	Total n=213 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Age, Categorical Between 18 and 65 years	49 Participants n=5 Participants	47 Participants n=7 Participants	32 Participants n=5 Participants	36 Participants n=4 Participants	10 Participants n=21 Participants	174 Participants n=8 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	3 Participants n=7 Participants	18 Participants n=5 Participants	16 Participants n=4 Participants	0 Participants n=21 Participants	39 Participants n=8 Participants
Age, Continuous	55.2 years STANDARD_DEVIATION 7.0 • n=5 Participants	54.6 years STANDARD_DEVIATION 7.6 • n=7 Participants	55.9 years STANDARD_DEVIATION 16.1 • n=5 Participants	55.9 years STANDARD_DEVIATION 12.2 • n=4 Participants	51.4 years STANDARD_DEVIATION 8.3 • n=21 Participants	55.4 years STANDARD_DEVIATION 11.3 • n=8 Participants
Sex: Female, Male Female	29 Participants n=5 Participants	30 Participants n=7 Participants	24 Participants n=5 Participants	19 Participants n=4 Participants	7 Participants n=21 Participants	109 Participants n=8 Participants
Sex: Female, Male Male	22 Participants n=5 Participants	20 Participants n=7 Participants	26 Participants n=5 Participants	33 Participants n=4 Participants	3 Participants n=21 Participants	104 Participants n=8 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	5 Participants n=8 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	0 Participants n=4 Participants	10 Participants n=21 Participants	16 Participants n=8 Participants
Race (NIH/OMB) White	46 Participants n=5 Participants	43 Participants n=7 Participants	45 Participants n=5 Participants	47 Participants n=4 Participants	0 Participants n=21 Participants	181 Participants n=8 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	3 Participants n=8 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants	0 Participants n=21 Participants	8 Participants n=8 Participants
Region of Enrollment United States	51 participants n=5 Participants	50 participants n=7 Participants	50 participants n=5 Participants	52 participants n=4 Participants	10 participants n=21 Participants	213 participants n=8 Participants

PRIMARY outcome

Timeframe: Change at 6-weeks post-results disclosure relative to baseline, administered approx.12.5 months after baseline

Population: Participants who completed the baseline survey and 6 week follow-up survey

Adapted measures (Hall, MA, et al. 2006) assessed participants' attitudes toward genetic information, trust of their physicians and the medical system regarding interpretation and use of genetic information. Higher scores on a 12-60 scale represent more positive attitudes and greater trust.

Outcome measures

Outcome measures
Measure	Family History + Whole Genome Sequencing: Primary Care n=50 Participants Doctors and their patients receive a Genome Report and an Annotated Family History Report. Main Study Experimental: Family History + Whole Genome Sequencing (Genome Report): Doctors and their patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient. Extension Phase: Experimental: Family History + Whole Genome Sequencing (Genome Report) \*In the main study participants are randomized between Experimental and Comparator, in the Extension phase of the study all participants are in the Experimental Arm.	Family History Only: Primary Care n=44 Participants Doctors and their patients receive an Annotated Family History Report only. Active Comparator: Standard of Care Only: Doctors and their patients receive a Family History report only	Family History + Whole Genome Sequencing - Cardiology n=48 Participants Doctors and their patients receive a Genome Report and an Annotated Family History Report. Main Study Experimental: Family History + Whole Genome Sequencing (Genome Report): Doctors and their patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient. Extension Phase: Experimental: Family History + Whole Genome Sequencing (Genome Report) \*In the main study participants are randomized between Experimental and Comparator Arms, in the Extension phase of the study all participants are in the Experimental Arm.	Family History Only: Cardiology n=46 Participants Doctors and their patients receive an Annotated Family History Report only. Active Comparator: Standard of Care Only: Doctors and their patients receive a Family History report only	Extension Cohort n=6 Participants Family History + Whole Genome Sequencing (Genome Report): Doctors and their African American patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient.
Change in Attitudes and Trust	0.0 units on a scale Standard Deviation 5.3	0.7 units on a scale Standard Deviation 4.5	3.5 units on a scale Standard Deviation 5.1	1.8 units on a scale Standard Deviation 3.5	1.0 units on a scale Standard Deviation 6.3

PRIMARY outcome

Timeframe: Baseline and 6-months post-results disclosure (6 mos. follow-up administered approx. 17 months after baseline)

Population: Participants randomized to the experimental Family History + Whole Genome Sequencing arm who completed both the baseline and the 6-month follow-up surveys

Assessed through a scale developed for the Multiplex Initiative (Kaphingst, K.A., et al. 2012). Higher scores on a 0-24 scale indicate greater confidence in participants' abilities to understand genetic information.

Outcome measures

Outcome measures
Measure	Family History + Whole Genome Sequencing: Primary Care n=49 Participants Doctors and their patients receive a Genome Report and an Annotated Family History Report. Main Study Experimental: Family History + Whole Genome Sequencing (Genome Report): Doctors and their patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient. Extension Phase: Experimental: Family History + Whole Genome Sequencing (Genome Report) \*In the main study participants are randomized between Experimental and Comparator, in the Extension phase of the study all participants are in the Experimental Arm.	Family History Only: Primary Care n=47 Participants Doctors and their patients receive an Annotated Family History Report only. Active Comparator: Standard of Care Only: Doctors and their patients receive a Family History report only	Family History + Whole Genome Sequencing - Cardiology n=7 Participants Doctors and their patients receive a Genome Report and an Annotated Family History Report. Main Study Experimental: Family History + Whole Genome Sequencing (Genome Report): Doctors and their patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient. Extension Phase: Experimental: Family History + Whole Genome Sequencing (Genome Report) \*In the main study participants are randomized between Experimental and Comparator Arms, in the Extension phase of the study all participants are in the Experimental Arm.	Family History Only: Cardiology Doctors and their patients receive an Annotated Family History Report only. Active Comparator: Standard of Care Only: Doctors and their patients receive a Family History report only	Extension Cohort Family History + Whole Genome Sequencing (Genome Report): Doctors and their African American patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient.
Change in Self Efficacy	0.3 units on a scale Standard Deviation 3.4	0.5 units on a scale Standard Deviation 4.3	3.1 units on a scale Standard Deviation 5.7	—	—

PRIMARY outcome

Timeframe: Baseline and 6-weeks post-disclosure (6 wks follow-up administered approx. 12.5 mos. after baseline)

Population: Participants who completed both the baseline and 6-week follow-up surveys

Through nine novel survey items, participants were asked about their preferences for the types of genetic testing results they would like to receive from their whole genome sequence. Scores on an 0-9 scale represent the change in the number of categories of types of genetic testing results out of 9 that participants wanted to learn about from Baseline to 6-weeks follow-up.

Outcome measures

Outcome measures
Measure	Family History + Whole Genome Sequencing: Primary Care n=48 Participants Doctors and their patients receive a Genome Report and an Annotated Family History Report. Main Study Experimental: Family History + Whole Genome Sequencing (Genome Report): Doctors and their patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient. Extension Phase: Experimental: Family History + Whole Genome Sequencing (Genome Report) \*In the main study participants are randomized between Experimental and Comparator, in the Extension phase of the study all participants are in the Experimental Arm.	Family History Only: Primary Care n=42 Participants Doctors and their patients receive an Annotated Family History Report only. Active Comparator: Standard of Care Only: Doctors and their patients receive a Family History report only	Family History + Whole Genome Sequencing - Cardiology n=47 Participants Doctors and their patients receive a Genome Report and an Annotated Family History Report. Main Study Experimental: Family History + Whole Genome Sequencing (Genome Report): Doctors and their patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient. Extension Phase: Experimental: Family History + Whole Genome Sequencing (Genome Report) \*In the main study participants are randomized between Experimental and Comparator Arms, in the Extension phase of the study all participants are in the Experimental Arm.	Family History Only: Cardiology n=44 Participants Doctors and their patients receive an Annotated Family History Report only. Active Comparator: Standard of Care Only: Doctors and their patients receive a Family History report only	Extension Cohort n=6 Participants Family History + Whole Genome Sequencing (Genome Report): Doctors and their African American patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient.
Change in Preferences for WGS Information	-.1 units on a scale Standard Deviation 1.5	0.2 units on a scale Standard Deviation 2.1	0 units on a scale Standard Deviation 2.0	.4 units on a scale Standard Deviation 2.3	0.0 units on a scale Standard Deviation 1.9

PRIMARY outcome

Timeframe: Baseline, at the disclosure visit (about 1 hour after results disclosure, avg. 11 mos. after baseline) and 6-months post-disclosure (6 mos. follow-up follow-up administered approx. 17 months after baseline)

Population: Participants who completed the item on patient surveys.

A single-item measure assessed how participants perceived their own health on a 1-5 scale. Adapted from the SF-12 (DeSalvo KB, Qual Life Res, 2006). Higher scores indicate more positive perceptions of health at follow-up

Outcome measures

Outcome measures
Measure	Family History + Whole Genome Sequencing: Primary Care n=50 Participants Doctors and their patients receive a Genome Report and an Annotated Family History Report. Main Study Experimental: Family History + Whole Genome Sequencing (Genome Report): Doctors and their patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient. Extension Phase: Experimental: Family History + Whole Genome Sequencing (Genome Report) \*In the main study participants are randomized between Experimental and Comparator, in the Extension phase of the study all participants are in the Experimental Arm.	Family History Only: Primary Care n=49 Participants Doctors and their patients receive an Annotated Family History Report only. Active Comparator: Standard of Care Only: Doctors and their patients receive a Family History report only	Family History + Whole Genome Sequencing - Cardiology n=49 Participants Doctors and their patients receive a Genome Report and an Annotated Family History Report. Main Study Experimental: Family History + Whole Genome Sequencing (Genome Report): Doctors and their patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient. Extension Phase: Experimental: Family History + Whole Genome Sequencing (Genome Report) \*In the main study participants are randomized between Experimental and Comparator Arms, in the Extension phase of the study all participants are in the Experimental Arm.	Family History Only: Cardiology n=51 Participants Doctors and their patients receive an Annotated Family History Report only. Active Comparator: Standard of Care Only: Doctors and their patients receive a Family History report only	Extension Cohort n=8 Participants Family History + Whole Genome Sequencing (Genome Report): Doctors and their African American patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient.
Change in Perceived Health Change at disclosure	-0.1 units on a scale Standard Deviation 0.6	0 units on a scale Standard Deviation 0.6	0 units on a scale Standard Deviation 0.6	-0.2 units on a scale Standard Deviation 0.7	0.3 units on a scale Standard Deviation 0.5
Change in Perceived Health Change at 6 months post-disclosure	-0.1 units on a scale Standard Deviation 0.7	-0.1 units on a scale Standard Deviation 0.7	-0.1 units on a scale Standard Deviation 0.8	-0.3 units on a scale Standard Deviation 0.8	0.1 units on a scale Standard Deviation 0.4

PRIMARY outcome

Timeframe: Baseline and 6-weeks post-disclosure (6 wks follow-up administered approx. 12.5 mos. after baseline)

Population: Participants who were completed the item on both the baseline and 6-week follow-up surveys

Changes in shared decision making were assessed through a single item adapted from the Control Preferences Scale, a measure designed to ascertain the degree of control an individual wants to assume when decisions are being made about medical treatment. Higher scores on a scale of 1-3 indicate preferences towards more equally shared decision making (Heisler et al 2003). Higher mean changes over time indicate a change in preference towards more equally shared decision making at follow-up.

Outcome measures

Outcome measures
Measure	Family History + Whole Genome Sequencing: Primary Care n=46 Participants Doctors and their patients receive a Genome Report and an Annotated Family History Report. Main Study Experimental: Family History + Whole Genome Sequencing (Genome Report): Doctors and their patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient. Extension Phase: Experimental: Family History + Whole Genome Sequencing (Genome Report) \*In the main study participants are randomized between Experimental and Comparator, in the Extension phase of the study all participants are in the Experimental Arm.	Family History Only: Primary Care n=41 Participants Doctors and their patients receive an Annotated Family History Report only. Active Comparator: Standard of Care Only: Doctors and their patients receive a Family History report only	Family History + Whole Genome Sequencing - Cardiology n=46 Participants Doctors and their patients receive a Genome Report and an Annotated Family History Report. Main Study Experimental: Family History + Whole Genome Sequencing (Genome Report): Doctors and their patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient. Extension Phase: Experimental: Family History + Whole Genome Sequencing (Genome Report) \*In the main study participants are randomized between Experimental and Comparator Arms, in the Extension phase of the study all participants are in the Experimental Arm.	Family History Only: Cardiology n=45 Participants Doctors and their patients receive an Annotated Family History Report only. Active Comparator: Standard of Care Only: Doctors and their patients receive a Family History report only	Extension Cohort n=5 Participants Family History + Whole Genome Sequencing (Genome Report): Doctors and their African American patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient.
Change in Shared Decision Making	0.1 units on a scale Standard Deviation 0.7	0 units on a scale Standard Deviation 0.5	0.2 units on a scale Standard Deviation 0.8	0.1 units on a scale Standard Deviation 0.7	-0.2 units on a scale Standard Deviation 0.8

PRIMARY outcome

Timeframe: Baseline and 6-months post-disclosure (6 mos. follow-up administered approx. 17 mos. after baseline)

Population: Participants who completed both the baseline and 6-month follow-up surveys

Changes in participants' tolerance for uncertainty were assessed through a short 12-item version of the Intolerance of Uncertainty Scale (Carleton, 2007). Total summed scale range is 12-60, with higher scores indicating increased negative feelings about uncertainty from baseline to follow-up.

Outcome measures

Outcome measures
Measure	Family History + Whole Genome Sequencing: Primary Care n=49 Participants Doctors and their patients receive a Genome Report and an Annotated Family History Report. Main Study Experimental: Family History + Whole Genome Sequencing (Genome Report): Doctors and their patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient. Extension Phase: Experimental: Family History + Whole Genome Sequencing (Genome Report) \*In the main study participants are randomized between Experimental and Comparator, in the Extension phase of the study all participants are in the Experimental Arm.	Family History Only: Primary Care n=44 Participants Doctors and their patients receive an Annotated Family History Report only. Active Comparator: Standard of Care Only: Doctors and their patients receive a Family History report only	Family History + Whole Genome Sequencing - Cardiology n=47 Participants Doctors and their patients receive a Genome Report and an Annotated Family History Report. Main Study Experimental: Family History + Whole Genome Sequencing (Genome Report): Doctors and their patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient. Extension Phase: Experimental: Family History + Whole Genome Sequencing (Genome Report) \*In the main study participants are randomized between Experimental and Comparator Arms, in the Extension phase of the study all participants are in the Experimental Arm.	Family History Only: Cardiology n=49 Participants Doctors and their patients receive an Annotated Family History Report only. Active Comparator: Standard of Care Only: Doctors and their patients receive a Family History report only	Extension Cohort n=7 Participants Family History + Whole Genome Sequencing (Genome Report): Doctors and their African American patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient.
Change in Intolerance of Uncertainty	-0.5 units on a scale Standard Deviation 6.3	0.3 units on a scale Standard Deviation 6.6	-1.3 units on a scale Standard Deviation 5.8	0 units on a scale Standard Deviation 7.4	4.9 units on a scale Standard Deviation 14.4

PRIMARY outcome

Timeframe: Baseline, at the disclosure visit (about 1 hour after results disclosure, avg. 11 mos. after baseline), 6-weeks post-disclosure and 6-months post-disclosure (6 wks. follow-up administered approx. 12.5 mos and 6 mos follow-up approx 17 mos. after baseline)

Population: Participants who completed the baseline survey and follow-up surveys

The Hospital Anxiety and Depression Scale (HADS) scale was administered through a survey. This is a validated scale designed to assess the participants' level of depression and anxiety through Likert-type questions. Total ranges for each summed subscale, anxiety and depression, is 0-21. Any participant scoring \>14 on the anxiety subscale or \>16 on the depression subscale were contacted by study staff for evaluation. Higher scores indicate increased anxiety or depression from baseline to follow-up.

Outcome measures

Outcome measures
Measure	Family History + Whole Genome Sequencing: Primary Care n=50 Participants Doctors and their patients receive a Genome Report and an Annotated Family History Report. Main Study Experimental: Family History + Whole Genome Sequencing (Genome Report): Doctors and their patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient. Extension Phase: Experimental: Family History + Whole Genome Sequencing (Genome Report) \*In the main study participants are randomized between Experimental and Comparator, in the Extension phase of the study all participants are in the Experimental Arm.	Family History Only: Primary Care n=49 Participants Doctors and their patients receive an Annotated Family History Report only. Active Comparator: Standard of Care Only: Doctors and their patients receive a Family History report only	Family History + Whole Genome Sequencing - Cardiology n=49 Participants Doctors and their patients receive a Genome Report and an Annotated Family History Report. Main Study Experimental: Family History + Whole Genome Sequencing (Genome Report): Doctors and their patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient. Extension Phase: Experimental: Family History + Whole Genome Sequencing (Genome Report) \*In the main study participants are randomized between Experimental and Comparator Arms, in the Extension phase of the study all participants are in the Experimental Arm.	Family History Only: Cardiology n=51 Participants Doctors and their patients receive an Annotated Family History Report only. Active Comparator: Standard of Care Only: Doctors and their patients receive a Family History report only	Extension Cohort n=8 Participants Family History + Whole Genome Sequencing (Genome Report): Doctors and their African American patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient.
Change in General Anxiety and Depression Change in Anxiety at disclosure	0.1 units on a scale Standard Deviation 2.3	-.2 units on a scale Standard Deviation 2.8	-.4 units on a scale Standard Deviation 1.9	-.3 units on a scale Standard Deviation 2.8	-0.5 units on a scale Standard Deviation 1.5
Change in General Anxiety and Depression Change in Anxiety at 6 Weeks	-1.4 units on a scale Standard Deviation 3.2	-.8 units on a scale Standard Deviation 2.3	-1.7 units on a scale Standard Deviation 2.6	-1.0 units on a scale Standard Deviation 2.4	-1.5 units on a scale Standard Deviation 1.5
Change in General Anxiety and Depression Change in Anxiety at 6 Months	-.2 units on a scale Standard Deviation 2.6	-.1 units on a scale Standard Deviation 2.6	-.2 units on a scale Standard Deviation 2.4	-.4 units on a scale Standard Deviation 2.4	-0.9 units on a scale Standard Deviation 3.0
Change in General Anxiety and Depression Change in Depression at disclosure	0 units on a scale Standard Deviation 2.1	0.7 units on a scale Standard Deviation 2.6	-0.1 units on a scale Standard Deviation 1.6	0 units on a scale Standard Deviation 2.0	-0.3 units on a scale Standard Deviation 2.8
Change in General Anxiety and Depression Change in Depression at 6 Weeks	-.3 units on a scale Standard Deviation 2.1	0.4 units on a scale Standard Deviation 2.7	-.8 units on a scale Standard Deviation 1.7	-.2 units on a scale Standard Deviation 1.8	-1.0 units on a scale Standard Deviation 2.8
Change in General Anxiety and Depression Change in Depression at 6 Months	-.1 units on a scale Standard Deviation 1.9	0.5 units on a scale Standard Deviation 2.1	-.1 units on a scale Standard Deviation 1.9	0 units on a scale Standard Deviation 1.8	0.9 units on a scale Standard Deviation 3.8

PRIMARY outcome

Timeframe: 6-weeks post-disclosure and 6-months post-disclosure (6 wks. follow-up administered approx. 12.5 mos. and 6 mos. follow-up approx. 17 mos. after baseline)

Population: Participants who attended disclosure sessions and responded to post-disclosure surveys

Novel items that asked whether participants changed vitamin use, supplement use, medication use, diet, exercise, or "other" health behaviors. Counts and percentages represent participants who reported any health behavior changes.

Outcome measures

Outcome measures
Measure	Family History + Whole Genome Sequencing: Primary Care n=50 Participants Doctors and their patients receive a Genome Report and an Annotated Family History Report. Main Study Experimental: Family History + Whole Genome Sequencing (Genome Report): Doctors and their patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient. Extension Phase: Experimental: Family History + Whole Genome Sequencing (Genome Report) \*In the main study participants are randomized between Experimental and Comparator, in the Extension phase of the study all participants are in the Experimental Arm.	Family History Only: Primary Care n=44 Participants Doctors and their patients receive an Annotated Family History Report only. Active Comparator: Standard of Care Only: Doctors and their patients receive a Family History report only	Family History + Whole Genome Sequencing - Cardiology n=48 Participants Doctors and their patients receive a Genome Report and an Annotated Family History Report. Main Study Experimental: Family History + Whole Genome Sequencing (Genome Report): Doctors and their patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient. Extension Phase: Experimental: Family History + Whole Genome Sequencing (Genome Report) \*In the main study participants are randomized between Experimental and Comparator Arms, in the Extension phase of the study all participants are in the Experimental Arm.	Family History Only: Cardiology n=49 Participants Doctors and their patients receive an Annotated Family History Report only. Active Comparator: Standard of Care Only: Doctors and their patients receive a Family History report only	Extension Cohort n=7 Participants Family History + Whole Genome Sequencing (Genome Report): Doctors and their African American patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient.
Change in Health Behaviors 6 Weeks Post-Disclosure	24 Participants	16 Participants	17 Participants	15 Participants	4 Participants
Change in Health Behaviors 6 Months Post-Disclosure	20 Participants	13 Participants	26 Participants	20 Participants	3 Participants

PRIMARY outcome

Timeframe: At the disclosure visit (about 1 hour after results disclosure, avg. 11 mos. after baseline) and 6-months post-disclosure (approx. 17 mos. after baseline)

Population: Participants who answered information-sharing questions on the post-disclosure or 6-month follow-up questionnaire

Sharing of information was assessed by asking patients if they intended to share results with others (at the end of the disclosure visit) and if they had shared their results with others (6 months after disclosure) adapted from the Health Information National Trends Survey (HINTS).

Outcome measures

Outcome measures
Measure	Family History + Whole Genome Sequencing: Primary Care n=46 Participants Doctors and their patients receive a Genome Report and an Annotated Family History Report. Main Study Experimental: Family History + Whole Genome Sequencing (Genome Report): Doctors and their patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient. Extension Phase: Experimental: Family History + Whole Genome Sequencing (Genome Report) \*In the main study participants are randomized between Experimental and Comparator, in the Extension phase of the study all participants are in the Experimental Arm.	Family History Only: Primary Care n=47 Participants Doctors and their patients receive an Annotated Family History Report only. Active Comparator: Standard of Care Only: Doctors and their patients receive a Family History report only	Family History + Whole Genome Sequencing - Cardiology n=43 Participants Doctors and their patients receive a Genome Report and an Annotated Family History Report. Main Study Experimental: Family History + Whole Genome Sequencing (Genome Report): Doctors and their patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient. Extension Phase: Experimental: Family History + Whole Genome Sequencing (Genome Report) \*In the main study participants are randomized between Experimental and Comparator Arms, in the Extension phase of the study all participants are in the Experimental Arm.	Family History Only: Cardiology n=45 Participants Doctors and their patients receive an Annotated Family History Report only. Active Comparator: Standard of Care Only: Doctors and their patients receive a Family History report only	Extension Cohort n=7 Participants Family History + Whole Genome Sequencing (Genome Report): Doctors and their African American patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient.
Information Sharing Plans to share at disclosure	43 Participants	39 Participants	42 Participants	30 Participants	6 Participants
Information Sharing Shared, per 6 month survey	41 Participants	27 Participants	38 Participants	28 Participants	4 Participants

PRIMARY outcome

Timeframe: Assessing Genomic Literacy at baseline and 6-months post-disclosure (approx. 17 mos. after baseline)

Population: Participants who completed the genetic literacy items in the baseline and 6-month follow-up surveys

Changes in participants' genomic literacy were measured with an 11-item measure adapted from the ClinSeq Study (Kaphingst K.A. et al. 2012) administered at baseline and 6 months post-disclosure. Items are marked as correct (1) or incorrect (0) and summed for a total scale range of 0 to 11, with higher scores indicating higher genomic literacy.

Outcome measures

Outcome measures
Measure	Family History + Whole Genome Sequencing: Primary Care n=50 Participants Doctors and their patients receive a Genome Report and an Annotated Family History Report. Main Study Experimental: Family History + Whole Genome Sequencing (Genome Report): Doctors and their patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient. Extension Phase: Experimental: Family History + Whole Genome Sequencing (Genome Report) \*In the main study participants are randomized between Experimental and Comparator, in the Extension phase of the study all participants are in the Experimental Arm.	Family History Only: Primary Care n=45 Participants Doctors and their patients receive an Annotated Family History Report only. Active Comparator: Standard of Care Only: Doctors and their patients receive a Family History report only	Family History + Whole Genome Sequencing - Cardiology n=47 Participants Doctors and their patients receive a Genome Report and an Annotated Family History Report. Main Study Experimental: Family History + Whole Genome Sequencing (Genome Report): Doctors and their patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient. Extension Phase: Experimental: Family History + Whole Genome Sequencing (Genome Report) \*In the main study participants are randomized between Experimental and Comparator Arms, in the Extension phase of the study all participants are in the Experimental Arm.	Family History Only: Cardiology n=49 Participants Doctors and their patients receive an Annotated Family History Report only. Active Comparator: Standard of Care Only: Doctors and their patients receive a Family History report only	Extension Cohort n=7 Participants Family History + Whole Genome Sequencing (Genome Report): Doctors and their African American patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient.
Changes in Genomic Literacy	-.4 units on a scale Standard Deviation 1.8	-.5 units on a scale Standard Deviation 2.3	-.6 units on a scale Standard Deviation 2.1	-.2 units on a scale Standard Deviation 1.2	0.0 units on a scale Standard Deviation 1.6

PRIMARY outcome

Timeframe: 6 months prior to disclosure and 6-months post-disclosure (approx. 17 mos. after baseline) and 5-years post-disclosure

Population: All randomized participants who received disclosure

Participants' health care utilization was assessed through a combination of medical record reviews and novel and adapted measures from the Behavioral Risk Factor Surveillance System (BRFSS). Changes are assessed by comparing the number of services and procedures received in 6 months following disclosure against the number of services and procedures received in the 6 months prior to disclosure.

Outcome measures

Outcome measures
Measure	Family History + Whole Genome Sequencing: Primary Care n=50 Participants Doctors and their patients receive a Genome Report and an Annotated Family History Report. Main Study Experimental: Family History + Whole Genome Sequencing (Genome Report): Doctors and their patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient. Extension Phase: Experimental: Family History + Whole Genome Sequencing (Genome Report) \*In the main study participants are randomized between Experimental and Comparator, in the Extension phase of the study all participants are in the Experimental Arm.	Family History Only: Primary Care n=50 Participants Doctors and their patients receive an Annotated Family History Report only. Active Comparator: Standard of Care Only: Doctors and their patients receive a Family History report only	Family History + Whole Genome Sequencing - Cardiology n=49 Participants Doctors and their patients receive a Genome Report and an Annotated Family History Report. Main Study Experimental: Family History + Whole Genome Sequencing (Genome Report): Doctors and their patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient. Extension Phase: Experimental: Family History + Whole Genome Sequencing (Genome Report) \*In the main study participants are randomized between Experimental and Comparator Arms, in the Extension phase of the study all participants are in the Experimental Arm.	Family History Only: Cardiology n=51 Participants Doctors and their patients receive an Annotated Family History Report only. Active Comparator: Standard of Care Only: Doctors and their patients receive a Family History report only	Extension Cohort n=10 Participants Family History + Whole Genome Sequencing (Genome Report): Doctors and their African American patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient.
Changes in Health Care Utilization Visits	3.9 units on a scale Standard Deviation 7.9	2.3 units on a scale Standard Deviation 6.8	1.7 units on a scale Standard Deviation 7.8	1.7 units on a scale Standard Deviation 7.1	0.6 units on a scale Standard Deviation 3.7
Changes in Health Care Utilization Labs	1.4 units on a scale Standard Deviation 8.9	-0.3 units on a scale Standard Deviation 7.8	1.5 units on a scale Standard Deviation 10.6	1.5 units on a scale Standard Deviation 7.4	0.5 units on a scale Standard Deviation 1.2
Changes in Health Care Utilization Imaging tests	0 units on a scale Standard Deviation 2.1	-.1 units on a scale Standard Deviation 2.6	0.9 units on a scale Standard Deviation 2.1	1.0 units on a scale Standard Deviation 1.7	0.0 units on a scale Standard Deviation 0.0
Changes in Health Care Utilization Cardiology tests	0.2 units on a scale Standard Deviation 1.0	0.2 units on a scale Standard Deviation 0.8	0.8 units on a scale Standard Deviation 2.7	0.9 units on a scale Standard Deviation 3.0	0.3 units on a scale Standard Deviation 0.6
Changes in Health Care Utilization Hospitalizations	0 units on a scale Standard Deviation 0.1	0 units on a scale Standard Deviation 0.2	0.1 units on a scale Standard Deviation 0.6	0.1 units on a scale Standard Deviation 0.7	0.0 units on a scale Standard Deviation 0.0

PRIMARY outcome

Timeframe: At baseline and 6-months post-disclosure (approx. 17 mos. after baseline)

Population: Participants who received whole genome sequencing and completed the survey items at baseline and at 6 months

A novel survey item asked participants to rate the usefulness of whole genome sequencing results for managing health on a 1-10 scale. Scores at 6 months were compared to scores at baseline.

Outcome measures

Outcome measures
Measure	Family History + Whole Genome Sequencing: Primary Care n=48 Participants Doctors and their patients receive a Genome Report and an Annotated Family History Report. Main Study Experimental: Family History + Whole Genome Sequencing (Genome Report): Doctors and their patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient. Extension Phase: Experimental: Family History + Whole Genome Sequencing (Genome Report) \*In the main study participants are randomized between Experimental and Comparator, in the Extension phase of the study all participants are in the Experimental Arm.	Family History Only: Primary Care n=45 Participants Doctors and their patients receive an Annotated Family History Report only. Active Comparator: Standard of Care Only: Doctors and their patients receive a Family History report only	Family History + Whole Genome Sequencing - Cardiology n=7 Participants Doctors and their patients receive a Genome Report and an Annotated Family History Report. Main Study Experimental: Family History + Whole Genome Sequencing (Genome Report): Doctors and their patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient. Extension Phase: Experimental: Family History + Whole Genome Sequencing (Genome Report) \*In the main study participants are randomized between Experimental and Comparator Arms, in the Extension phase of the study all participants are in the Experimental Arm.	Family History Only: Cardiology Doctors and their patients receive an Annotated Family History Report only. Active Comparator: Standard of Care Only: Doctors and their patients receive a Family History report only	Extension Cohort Family History + Whole Genome Sequencing (Genome Report): Doctors and their African American patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient.
Change in Perceived Utility	-.6 units on a scale Standard Deviation 2.5	-.9 units on a scale Standard Deviation 3.0	-1.0 units on a scale Standard Deviation 2.3	—	—

SECONDARY outcome

Timeframe: 6-weeks post-disclosure and 6-months post-disclosure (6wks. follow-up administered approx. 12.5 mos. and 6 mos. follow-up approx. 17 mos. after baseline)

Population: Participants who answered the psychological impact items on the 6 week or 6 month follow-up questionnaires

Psychological impact was assessed by a modified version of the Multidimensional Impact of Cancer Risk Assessment (MICRA) questionnaire. Higher scores indicated more distress related to study results.

Outcome measures

Outcome measures
Measure	Family History + Whole Genome Sequencing: Primary Care n=46 Participants Doctors and their patients receive a Genome Report and an Annotated Family History Report. Main Study Experimental: Family History + Whole Genome Sequencing (Genome Report): Doctors and their patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient. Extension Phase: Experimental: Family History + Whole Genome Sequencing (Genome Report) \*In the main study participants are randomized between Experimental and Comparator, in the Extension phase of the study all participants are in the Experimental Arm.	Family History Only: Primary Care n=41 Participants Doctors and their patients receive an Annotated Family History Report only. Active Comparator: Standard of Care Only: Doctors and their patients receive a Family History report only	Family History + Whole Genome Sequencing - Cardiology n=45 Participants Doctors and their patients receive a Genome Report and an Annotated Family History Report. Main Study Experimental: Family History + Whole Genome Sequencing (Genome Report): Doctors and their patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient. Extension Phase: Experimental: Family History + Whole Genome Sequencing (Genome Report) \*In the main study participants are randomized between Experimental and Comparator Arms, in the Extension phase of the study all participants are in the Experimental Arm.	Family History Only: Cardiology n=44 Participants Doctors and their patients receive an Annotated Family History Report only. Active Comparator: Standard of Care Only: Doctors and their patients receive a Family History report only	Extension Cohort n=7 Participants Family History + Whole Genome Sequencing (Genome Report): Doctors and their African American patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient.
Psychological Impact 6 Weeks Post-Disclosure	13.2 units on a scale Standard Deviation 3.8	15.1 units on a scale Standard Deviation 3.9	14.2 units on a scale Standard Deviation 4.8	14.5 units on a scale Standard Deviation 4.3	11.4 units on a scale Standard Deviation 4.2
Psychological Impact 6 Months Post-Disclosure	14.9 units on a scale Standard Deviation 3.2	15.2 units on a scale Standard Deviation 3.7	16.0 units on a scale Standard Deviation 5.4	16.5 units on a scale Standard Deviation 5.6	14.1 units on a scale Standard Deviation 3.5

SECONDARY outcome

Timeframe: At post-disclosure visit (about 1 hour after results disclosure, avg. 11 mos. after baseline), at 6-weeks post-disclosure, and at 6-months post-disclosure (6 wks follow-up approx. 12.5 mos. and 6 mos. follow-up approx. 17 mos. after baseline)

Population: Participants who answered the decisional regret items on the post-disclosure, 6 week follow-up, or 6 month follow-up surveys

Participants' satisfaction with their decision to participate in the MedSeq Project through a 5-item validated scale (Brehaut 2003). Average score computed after reversing scores of 2 negatively phrased items and converting score to range from 0-100 by subtracting 1 and multiplying by 25. Higher scores indicate greater regret.

Outcome measures

Outcome measures
Measure	Family History + Whole Genome Sequencing: Primary Care n=50 Participants Doctors and their patients receive a Genome Report and an Annotated Family History Report. Main Study Experimental: Family History + Whole Genome Sequencing (Genome Report): Doctors and their patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient. Extension Phase: Experimental: Family History + Whole Genome Sequencing (Genome Report) \*In the main study participants are randomized between Experimental and Comparator, in the Extension phase of the study all participants are in the Experimental Arm.	Family History Only: Primary Care n=49 Participants Doctors and their patients receive an Annotated Family History Report only. Active Comparator: Standard of Care Only: Doctors and their patients receive a Family History report only	Family History + Whole Genome Sequencing - Cardiology n=49 Participants Doctors and their patients receive a Genome Report and an Annotated Family History Report. Main Study Experimental: Family History + Whole Genome Sequencing (Genome Report): Doctors and their patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient. Extension Phase: Experimental: Family History + Whole Genome Sequencing (Genome Report) \*In the main study participants are randomized between Experimental and Comparator Arms, in the Extension phase of the study all participants are in the Experimental Arm.	Family History Only: Cardiology n=51 Participants Doctors and their patients receive an Annotated Family History Report only. Active Comparator: Standard of Care Only: Doctors and their patients receive a Family History report only	Extension Cohort n=9 Participants Family History + Whole Genome Sequencing (Genome Report): Doctors and their African American patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient.
Decisional Regret Post-Disclosure	8.9 units on a scale Standard Deviation 16.7	12.9 units on a scale Standard Deviation 14.0	6.2 units on a scale Standard Deviation 9.6	15.8 units on a scale Standard Deviation 22.8	6.1 units on a scale Standard Deviation 10.8
Decisional Regret 6 Weeks Post-Disclosure	9.8 units on a scale Standard Deviation 16.6	17.2 units on a scale Standard Deviation 15.5	5.8 units on a scale Standard Deviation 9.7	15.0 units on a scale Standard Deviation 20.6	6.4 units on a scale Standard Deviation 11.1
Decisional Regret 6 Months Post-Disclosure	11.5 units on a scale Standard Deviation 18.2	19.9 units on a scale Standard Deviation 19.3	7.9 units on a scale Standard Deviation 11.2	11.3 units on a scale Standard Deviation 15.9	4.2 units on a scale Standard Deviation 10.2

SECONDARY outcome

Timeframe: At post-disclosure visit (about 1 hour after results disclosure, avg. 11 mos. after baseline), at 6-weeks post-disclosure, and at 6-months post-disclosure (6 wks follow-up approx. 12.5 mos. and 6 mos. follow-up approx. 17 mos. after baseline)

Population: Participants who answered the understanding item on the post-disclosure, 6-week follow-up, or 6-month follow-up surveys.

A novel item assessed participants' subjective understanding of their study results on a 1-5 scale, where higher scores indicate greater subjective understanding.

Outcome measures

Outcome measures
Measure	Family History + Whole Genome Sequencing: Primary Care n=50 Participants Doctors and their patients receive a Genome Report and an Annotated Family History Report. Main Study Experimental: Family History + Whole Genome Sequencing (Genome Report): Doctors and their patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient. Extension Phase: Experimental: Family History + Whole Genome Sequencing (Genome Report) \*In the main study participants are randomized between Experimental and Comparator, in the Extension phase of the study all participants are in the Experimental Arm.	Family History Only: Primary Care n=44 Participants Doctors and their patients receive an Annotated Family History Report only. Active Comparator: Standard of Care Only: Doctors and their patients receive a Family History report only	Family History + Whole Genome Sequencing - Cardiology n=49 Participants Doctors and their patients receive a Genome Report and an Annotated Family History Report. Main Study Experimental: Family History + Whole Genome Sequencing (Genome Report): Doctors and their patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient. Extension Phase: Experimental: Family History + Whole Genome Sequencing (Genome Report) \*In the main study participants are randomized between Experimental and Comparator Arms, in the Extension phase of the study all participants are in the Experimental Arm.	Family History Only: Cardiology n=49 Participants Doctors and their patients receive an Annotated Family History Report only. Active Comparator: Standard of Care Only: Doctors and their patients receive a Family History report only	Extension Cohort n=7 Participants Family History + Whole Genome Sequencing (Genome Report): Doctors and their African American patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient.
Understanding Post-Disclosure	4.2 units on a scale Standard Deviation 0.7	4.5 units on a scale Standard Deviation 0.7	4.0 units on a scale Standard Deviation 0.7	4.2 units on a scale Standard Deviation 0.8	3.9 units on a scale Standard Deviation 0.7
Understanding 6 Weeks Post-Disclosure	4.2 units on a scale Standard Deviation 0.8	4.2 units on a scale Standard Deviation 0.9	4.1 units on a scale Standard Deviation 0.7	4.2 units on a scale Standard Deviation 0.9	4.0 units on a scale Standard Deviation 0.6
Understanding 6 Months Post-Disclosure	4.0 units on a scale Standard Deviation 0.7	4.3 units on a scale Standard Deviation 0.7	4.0 units on a scale Standard Deviation 0.8	4.2 units on a scale Standard Deviation 0.7	4.0 units on a scale Standard Deviation 0.6

SECONDARY outcome

Timeframe: Baseline

Population: Randomized participants who completed the baseline survey.

Novel survey items asked participants about whether or not their genetic test results would be useful for specific reasons. Response options were "no," "probably not", "probably yes," and "yes." Responses of "probably yes" and "yes" were combined to simplify presentation of data.

Outcome measures

Outcome measures
Measure	Family History + Whole Genome Sequencing: Primary Care n=51 Participants Doctors and their patients receive a Genome Report and an Annotated Family History Report. Main Study Experimental: Family History + Whole Genome Sequencing (Genome Report): Doctors and their patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient. Extension Phase: Experimental: Family History + Whole Genome Sequencing (Genome Report) \*In the main study participants are randomized between Experimental and Comparator, in the Extension phase of the study all participants are in the Experimental Arm.	Family History Only: Primary Care n=49 Participants Doctors and their patients receive an Annotated Family History Report only. Active Comparator: Standard of Care Only: Doctors and their patients receive a Family History report only	Family History + Whole Genome Sequencing - Cardiology n=50 Participants Doctors and their patients receive a Genome Report and an Annotated Family History Report. Main Study Experimental: Family History + Whole Genome Sequencing (Genome Report): Doctors and their patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient. Extension Phase: Experimental: Family History + Whole Genome Sequencing (Genome Report) \*In the main study participants are randomized between Experimental and Comparator Arms, in the Extension phase of the study all participants are in the Experimental Arm.	Family History Only: Cardiology n=52 Participants Doctors and their patients receive an Annotated Family History Report only. Active Comparator: Standard of Care Only: Doctors and their patients receive a Family History report only	Extension Cohort n=10 Participants Family History + Whole Genome Sequencing (Genome Report): Doctors and their African American patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient.
Expectations Identify disease risk	40 Participants	36 Participants	41 Participants	42 Participants	8 Participants
Expectations Influence treatment	43 Participants	44 Participants	41 Participants	44 Participants	10 Participants
Expectations Influence medical care	44 Participants	46 Participants	40 Participants	44 Participants	9 Participants
Expectations Influence medications	35 Participants	41 Participants	36 Participants	35 Participants	10 Participants
Expectations Influence end-of-life planning	27 Participants	19 Participants	25 Participants	22 Participants	7 Participants
Expectations Influence reproductive decisions	18 Participants	8 Participants	24 Participants	16 Participants	4 Participants

Adverse Events

Family History + Whole Genome Sequencing: Primary Care

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Family History Only: Primary Care

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Family History + Whole Genome Sequencing: Cardiology

Serious events: 3 serious events

Other events: 0 other events

Deaths: 3 deaths

Family History Only: Cardiology

Serious events: 1 serious events

Other events: 0 other events

Deaths: 1 deaths

Extension Cohort

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Family History + Whole Genome Sequencing: Primary Care n=51 participants at risk Doctors and their patients receive a Genome Report and an Annotated Family History Report. Main Study Experimental: Family History + Whole Genome Sequencing (Genome Report): Doctors and their patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient. Extension Phase: Experimental: Family History + Whole Genome Sequencing (Genome Report) \*In the main study participants are randomized between Experimental and Comparator arms, in the Extension phase of the study all participants are in the Experimental Arm.	Family History Only: Primary Care n=50 participants at risk Doctors and their patients receive an Annotated Family History Report only. Active Comparator: Family History Only: Doctors and their patients receive a Family History report only.	Family History + Whole Genome Sequencing: Cardiology n=50 participants at risk Doctors and their patients receive a Genome Report and an Annotated Family History Report. Main Study Experimental: Family History + Whole Genome Sequencing (Genome Report): Doctors and their patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient. Extension Phase: Experimental: Family History + Whole Genome Sequencing (Genome Report) \*In the main study participants are randomized between Experimental and Comparator arms, in the Extension phase of the study all participants are in the Experimental Arm.	Family History Only: Cardiology n=52 participants at risk Doctors and their patients receive an Annotated Family History Report only. Active Comparator: Family History Only: Doctors and their patients receive a Family History report only	Extension Cohort n=10 participants at risk Family History + Whole Genome Sequencing (Genome Report): Doctors and their African American patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient.
Cardiac disorders Serious	0.00% 0/51 • Baseline to 6 months for the main cohort and through 5 years for the Long Term Follow-up cohort Adverse event definitions are consistant with clinicatrials.gov Adverse events were collected and reported to the IRB	0.00% 0/50 • Baseline to 6 months for the main cohort and through 5 years for the Long Term Follow-up cohort Adverse event definitions are consistant with clinicatrials.gov Adverse events were collected and reported to the IRB	6.0% 3/50 • Number of events 3 • Baseline to 6 months for the main cohort and through 5 years for the Long Term Follow-up cohort Adverse event definitions are consistant with clinicatrials.gov Adverse events were collected and reported to the IRB	1.9% 1/52 • Number of events 1 • Baseline to 6 months for the main cohort and through 5 years for the Long Term Follow-up cohort Adverse event definitions are consistant with clinicatrials.gov Adverse events were collected and reported to the IRB	0.00% 0/10 • Baseline to 6 months for the main cohort and through 5 years for the Long Term Follow-up cohort Adverse event definitions are consistant with clinicatrials.gov Adverse events were collected and reported to the IRB
Cardiac disorders Death	0.00% 0/51 • Baseline to 6 months for the main cohort and through 5 years for the Long Term Follow-up cohort Adverse event definitions are consistant with clinicatrials.gov Adverse events were collected and reported to the IRB	0.00% 0/50 • Baseline to 6 months for the main cohort and through 5 years for the Long Term Follow-up cohort Adverse event definitions are consistant with clinicatrials.gov Adverse events were collected and reported to the IRB	6.0% 3/50 • Baseline to 6 months for the main cohort and through 5 years for the Long Term Follow-up cohort Adverse event definitions are consistant with clinicatrials.gov Adverse events were collected and reported to the IRB	1.9% 1/52 • Baseline to 6 months for the main cohort and through 5 years for the Long Term Follow-up cohort Adverse event definitions are consistant with clinicatrials.gov Adverse events were collected and reported to the IRB	0.00% 0/10 • Baseline to 6 months for the main cohort and through 5 years for the Long Term Follow-up cohort Adverse event definitions are consistant with clinicatrials.gov Adverse events were collected and reported to the IRB

Other adverse events

Other adverse events
Measure	Family History + Whole Genome Sequencing: Primary Care n=51 participants at risk Doctors and their patients receive a Genome Report and an Annotated Family History Report. Main Study Experimental: Family History + Whole Genome Sequencing (Genome Report): Doctors and their patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient. Extension Phase: Experimental: Family History + Whole Genome Sequencing (Genome Report) \*In the main study participants are randomized between Experimental and Comparator arms, in the Extension phase of the study all participants are in the Experimental Arm.	Family History Only: Primary Care n=50 participants at risk Doctors and their patients receive an Annotated Family History Report only. Active Comparator: Family History Only: Doctors and their patients receive a Family History report only.	Family History + Whole Genome Sequencing: Cardiology n=50 participants at risk Doctors and their patients receive a Genome Report and an Annotated Family History Report. Main Study Experimental: Family History + Whole Genome Sequencing (Genome Report): Doctors and their patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: 1. The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. 2. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient. Extension Phase: Experimental: Family History + Whole Genome Sequencing (Genome Report) \*In the main study participants are randomized between Experimental and Comparator arms, in the Extension phase of the study all participants are in the Experimental Arm.	Family History Only: Cardiology n=52 participants at risk Doctors and their patients receive an Annotated Family History Report only. Active Comparator: Family History Only: Doctors and their patients receive a Family History report only	Extension Cohort n=10 participants at risk Family History + Whole Genome Sequencing (Genome Report): Doctors and their African American patients receive a Genome Report and a Family History Report. There are two sections of the Genome Report: The General Genome Report, which includes highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations. The Cardiac Risk Supplement, which contains genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient.
Psychiatric disorders Other	0.00% 0/51 • Baseline to 6 months for the main cohort and through 5 years for the Long Term Follow-up cohort Adverse event definitions are consistant with clinicatrials.gov Adverse events were collected and reported to the IRB	6.0% 3/50 • Number of events 3 • Baseline to 6 months for the main cohort and through 5 years for the Long Term Follow-up cohort Adverse event definitions are consistant with clinicatrials.gov Adverse events were collected and reported to the IRB	0.00% 0/50 • Baseline to 6 months for the main cohort and through 5 years for the Long Term Follow-up cohort Adverse event definitions are consistant with clinicatrials.gov Adverse events were collected and reported to the IRB	0.00% 0/52 • Baseline to 6 months for the main cohort and through 5 years for the Long Term Follow-up cohort Adverse event definitions are consistant with clinicatrials.gov Adverse events were collected and reported to the IRB	0.00% 0/10 • Baseline to 6 months for the main cohort and through 5 years for the Long Term Follow-up cohort Adverse event definitions are consistant with clinicatrials.gov Adverse events were collected and reported to the IRB

Additional Information

Carrie Blout, Genetic Counselor Project Manager

Brigham and Women's Hospital

Phone: 617-264-5837

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place