Polygenic Risk Score to Predict Weight Loss Intervention in Children With Obesity

NCT ID: NCT05466097

Last Updated: 2023-09-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

300 participants

Study Classification

OBSERVATIONAL

Study Start Date

2022-06-01

Study Completion Date

2025-07-31

Brief Summary

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Children with obesity are prone to suffering from metabolic diseases, which undoubtedly increases the burden of public health. Since obesity is a multiple gene disease, a comprehensive approach using polygenic risk scores (PRS), rather than individual genetic variant, may be a more appropriate method. The aim of the study was to establish a polygenic risk score model to assess differences to assess differences in weight loss treatment outcomes.

Detailed Description

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The investigators hypothesize that obesity gene variants can predict the efficacy of weight loss intervention in obese children. The aim of the study was to establish a polygenic risk score model to assess differences to assess differences in weight loss treatment outcomes. The investigators will also analyze whether these gene variants have an effect on obesity comorbidities (hypertension, hyperlipidemia, non-alcoholic fatty liver disease, type 2 diabetes, obstructive sleep apnea, polycystic ovary syndrome, etc.). For participants with non-simple obesity, the investigators will collect their complete family history, and perform whole exome sequencing to identify possible rare disease-causing genes.

The experimental design is as follows:

Obese children and adolescent subjects will undergo a 6-month weight loss intervention program and be followed for 12-18 months. The investigators will analyze obesity and fatty liver-related genes in these adolescents using next-generation gene sequencing and/or gene chips, perform polygenic risk score analysis, and use an additive model to total the number of variant loci weighted by effect size. Whole exome gene sequencing refers to the human DNA map (hg19), and Sanger sequencing will be used to confirm the correctness of the variant site.

Conditions

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Obesity Children

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Eligibility Criteria

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Inclusion Criteria

* Age \<18 years old
* Obesity definition: BMI \> 95% according to the age- and gender-specific standard by National Health Institute in Taiwan
* Willing to give written informed consent

Exclusion Criteria

* Alcohol consumption
* Major systemic diseases, including cardiopulmonary disease, renal failure, cancer, and major psychotic disorder
Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ministry of Science and Technology, Taiwan

OTHER_GOV

Sponsor Role collaborator

Far Eastern Memorial Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Yu-Cheng Lin,, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Far Eastern Memorial Hospital

Locations

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Far Eastern Memorial Hospital

New Taipei City, , Taiwan

Site Status RECRUITING

Countries

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Taiwan

Central Contacts

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Yu-Cheng Lin,, M.D., Ph.D.

Role: CONTACT

+886-89667000 Ext. 1723

Facility Contacts

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Yu-Cheng Lin, M.D., Ph.D.

Role: primary

886-89667000 ext. 1723

References

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Cali AM, Caprio S. Obesity in children and adolescents. J Clin Endocrinol Metab. 2008 Nov;93(11 Suppl 1):S31-6. doi: 10.1210/jc.2008-1363.

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PMID: 18987268 (View on PubMed)

El-Sayed Moustafa JS, Froguel P. From obesity genetics to the future of personalized obesity therapy. Nat Rev Endocrinol. 2013 Jul;9(7):402-13. doi: 10.1038/nrendo.2013.57. Epub 2013 Mar 26.

Reference Type BACKGROUND
PMID: 23529041 (View on PubMed)

Bradfield JP, Taal HR, Timpson NJ, Scherag A, Lecoeur C, Warrington NM, Hypponen E, Holst C, Valcarcel B, Thiering E, Salem RM, Schumacher FR, Cousminer DL, Sleiman PM, Zhao J, Berkowitz RI, Vimaleswaran KS, Jarick I, Pennell CE, Evans DM, St Pourcain B, Berry DJ, Mook-Kanamori DO, Hofman A, Rivadeneira F, Uitterlinden AG, van Duijn CM, van der Valk RJ, de Jongste JC, Postma DS, Boomsma DI, Gauderman WJ, Hassanein MT, Lindgren CM, Magi R, Boreham CA, Neville CE, Moreno LA, Elliott P, Pouta A, Hartikainen AL, Li M, Raitakari O, Lehtimaki T, Eriksson JG, Palotie A, Dallongeville J, Das S, Deloukas P, McMahon G, Ring SM, Kemp JP, Buxton JL, Blakemore AI, Bustamante M, Guxens M, Hirschhorn JN, Gillman MW, Kreiner-Moller E, Bisgaard H, Gilliland FD, Heinrich J, Wheeler E, Barroso I, O'Rahilly S, Meirhaeghe A, Sorensen TI, Power C, Palmer LJ, Hinney A, Widen E, Farooqi IS, McCarthy MI, Froguel P, Meyre D, Hebebrand J, Jarvelin MR, Jaddoe VW, Smith GD, Hakonarson H, Grant SF; Early Growth Genetics Consortium. A genome-wide association meta-analysis identifies new childhood obesity loci. Nat Genet. 2012 May;44(5):526-31. doi: 10.1038/ng.2247.

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Gurdasani D, Barroso I, Zeggini E, Sandhu MS. Genomics of disease risk in globally diverse populations. Nat Rev Genet. 2019 Sep;20(9):520-535. doi: 10.1038/s41576-019-0144-0. Epub 2019 Jun 24.

Reference Type BACKGROUND
PMID: 31235872 (View on PubMed)

Holzapfel C, Sag S, Graf-Schindler J, Fischer M, Drabsch T, Illig T, Grallert H, Stecher L, Strack C, Caterson ID, Jebb SA, Hauner H, Baessler A. Association between Single Nucleotide Polymorphisms and Weight Reduction in Behavioural Interventions-A Pooled Analysis. Nutrients. 2021 Mar 2;13(3):819. doi: 10.3390/nu13030819.

Reference Type BACKGROUND
PMID: 33801339 (View on PubMed)

Heitkamp M, Siegrist M, Molnos S, Brandmaier S, Wahl S, Langhof H, Grallert H, Halle M. Obesity Genes and Weight Loss During Lifestyle Intervention in Children With Obesity. JAMA Pediatr. 2021 Jan 1;175(1):e205142. doi: 10.1001/jamapediatrics.2020.5142. Epub 2021 Jan 4.

Reference Type BACKGROUND
PMID: 33315090 (View on PubMed)

Herrera BM, Lindgren CM. The genetics of obesity. Curr Diab Rep. 2010 Dec;10(6):498-505. doi: 10.1007/s11892-010-0153-z.

Reference Type BACKGROUND
PMID: 20931363 (View on PubMed)

Walley AJ, Asher JE, Froguel P. The genetic contribution to non-syndromic human obesity. Nat Rev Genet. 2009 Jul;10(7):431-42. doi: 10.1038/nrg2594.

Reference Type BACKGROUND
PMID: 19506576 (View on PubMed)

Wand H, Lambert SA, Tamburro C, Iacocca MA, O'Sullivan JW, Sillari C, Kullo IJ, Rowley R, Dron JS, Brockman D, Venner E, McCarthy MI, Antoniou AC, Easton DF, Hegele RA, Khera AV, Chatterjee N, Kooperberg C, Edwards K, Vlessis K, Kinnear K, Danesh JN, Parkinson H, Ramos EM, Roberts MC, Ormond KE, Khoury MJ, Janssens ACJW, Goddard KAB, Kraft P, MacArthur JAL, Inouye M, Wojcik GL. Improving reporting standards for polygenic scores in risk prediction studies. Nature. 2021 Mar;591(7849):211-219. doi: 10.1038/s41586-021-03243-6. Epub 2021 Mar 10.

Reference Type BACKGROUND
PMID: 33692554 (View on PubMed)

Eddowes PJ, Sasso M, Allison M, Tsochatzis E, Anstee QM, Sheridan D, Guha IN, Cobbold JF, Deeks JJ, Paradis V, Bedossa P, Newsome PN. Accuracy of FibroScan Controlled Attenuation Parameter and Liver Stiffness Measurement in Assessing Steatosis and Fibrosis in Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology. 2019 May;156(6):1717-1730. doi: 10.1053/j.gastro.2019.01.042. Epub 2019 Jan 25.

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PMID: 30689971 (View on PubMed)

Khera AV, Chaffin M, Wade KH, Zahid S, Brancale J, Xia R, Distefano M, Senol-Cosar O, Haas ME, Bick A, Aragam KG, Lander ES, Smith GD, Mason-Suares H, Fornage M, Lebo M, Timpson NJ, Kaplan LM, Kathiresan S. Polygenic Prediction of Weight and Obesity Trajectories from Birth to Adulthood. Cell. 2019 Apr 18;177(3):587-596.e9. doi: 10.1016/j.cell.2019.03.028.

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Ford AL, Hunt LP, Cooper A, Shield JP. What reduction in BMI SDS is required in obese adolescents to improve body composition and cardiometabolic health? Arch Dis Child. 2010 Apr;95(4):256-61. doi: 10.1136/adc.2009.165340. Epub 2009 Dec 4.

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Sun C, Kovacs P, Guiu-Jurado E. Genetics of Obesity in East Asians. Front Genet. 2020 Oct 20;11:575049. doi: 10.3389/fgene.2020.575049. eCollection 2020.

Reference Type BACKGROUND
PMID: 33193685 (View on PubMed)

Related Links

Access external resources that provide additional context or updates about the study.

https://doi.org/10.1038/nrendo.2013.57

From obesity genetics to the future of personalized obesity therapy

https://doi.org/10.1038/ng.2247

A genome-wide association meta-analysis identifies new childhood obesity loci

https://doi.org/10.1038/s41576-019-0144-0

Genomics of disease risk in globally diverse populations

https://doi.org/10.1038/nrg2594

The genetic contribution to non-syndromic human obesity

https://doi.org/10.1038/s41586-021-03243-6

Improving reporting standards for polygenic scores in risk prediction studies

https://doi.org/10.1053/j.gastro.2019.01.042

Accuracy of FibroScan Controlled Attenuation Parameter and Liver Stiffness Measurement in Assessing Steatosis and Fibrosis in Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology

https://doi.org/10.1016/j.cell.2019.03.028

Polygenic Prediction of Weight and Obesity Trajectories from Birth to Adulthood

https://doi.org/10.1136/adc.2009.165340

What reduction in BMI SDS is required in obese adolescents to improve body composition and cardiometabolic health?

https://doi.org/10.3389/fgene.2020.575049

Genetics of Obesity in East Asians

Other Identifiers

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111078-F

Identifier Type: -

Identifier Source: org_study_id

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