Optimal Approach for Analysis of Case-Control Genetic Association Studies

NCT ID: NCT00241709

Last Updated: 2013-03-11

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 800 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2005-08-31

Brief Summary

The purpose of this study is to examine the effectiveness of approaches to correct for the effects of population stratification on case-control genetic association studies.

Detailed Description

BACKGROUND:

In racially admixed populations, genetic associations may be confounded by population stratification. To control for population stratification, statistical methods that use marker genotype data to infer population structure have been proposed as an alternative to family-based tests of association. However, there are limited empirical data on how these methods perform in real populations. This study will use well characterized populations of Mexican and Puerto Rican asthmatics, their parents, and control subjects recruited from the same sites to examine the effectiveness of approaches to correct for the effects of population stratification on case-control genetic association studies.

DESIGN NARRATIVE:

This study has three specific aims: 1) To test and compare methods of detecting and correcting for population stratification, the study will genotype a total of 100 ancestral informative markers (AIMs) for 400 asthma cases and an equal number of control subjects. These AIMs will then be used with three statistical methods developed to detect and correct for population stratification. The number and characteristics of markers required to correct false positive associations between AIMs, asthma, and asthma quantitative traits will be evaluated and compared; 2) To compare the power of genomically adjusted case-control studies to the Transmission Disequilibrium Test (TDT). An allele from each of the 100 AIMs will be considered as a risk factor for a simulated "phenotype." The association between phenotypes and each AIM will be tested with the TDT and with a case-control analysis after adjustment for stratification to compare the false negative rates for these study designs. 3) To use the results from aim 1 and 2 to define an optimal approach for analysis and interpretation of case-control association studies in these populations and apply this approach to analyze the association between asthma and a series of candidate genes. The results of these studies should provide important insights into optimal methods to control for population stratification in case-control association studies, thereby facilitating the inclusion of admixed populations in future genetic studies of complex diseases such as asthma.

Conditions

Lung Diseases; Asthma

Study Design

• Observational Model Type: FAMILY_BASED
• Study Time Perspective: RETROSPECTIVE

Eligibility Criteria

Inclusion Criteria

No eligibility criteria; this study will be using existing blood samples of Mexican and Puerto Rican asthmatics, their parents, and control participants who were recruited prior to the study.

• Minimum Eligible Age: 8 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Esteban Gonzalez Burchard, MD

Role: PRINCIPAL_INVESTIGATOR

University of California School of Medicine, San Francisco

Locations

University of California, San Francisco

San Francisco, California, United States

Countries

United States

Other Identifiers

R01HL078885

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1309

Identifier Type: -

Identifier Source: org_study_id