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Circ Cardiovasc Genet DOI:10.1161/CIRCGENETICS.109.882696

Candidate gene association resource (CARe): design, methods, and proof of concept.

Publication TypeJournal Article
Year of Publication2010
AuthorsMusunuru, K, Lettre, G, Young, T, Farlow, DN, Pirruccello, JP, Ejebe, KG, Keating, BJ, Yang, Q, Chen, M-H, Lapchyk, N, Crenshaw, A, Ziaugra, L, Rachupka, A, Benjamin, EJ, L Cupples, A, Fornage, M, Fox, ER, Heckbert, SR, Hirschhorn, JN, Newton-Cheh, C, Nizzari, MM, Paltoo, DN, Papanicolaou, GJ, Patel, SR, Psaty, BM, Rader, DJ, Redline, S, Rich, SS, Rotter, JI, Taylor, HA, Tracy, RP, Vasan, RS, Wilson, JG, Kathiresan, S, Fabsitz, RR, Boerwinkle, E, Gabriel, SB
Corporate AuthorsNHLBI Candidate Gene Association Resource
JournalCirc Cardiovasc Genet
Volume3
Issue3
Pages267-75
Date Published2010 Jun
ISSN1942-3268
KeywordsAfrican Americans, Cholesterol, HDL, Cholesterol, LDL, Cohort Studies, Databases, Genetic, European Continental Ancestry Group, Genetic Association Studies, Genotype, Humans, Phenotype, Pilot Projects, Polymorphism, Single Nucleotide, Research Design, Triglycerides
Abstract

BACKGROUND: The National Heart, Lung, and Blood Institute's Candidate Gene Association Resource (CARe), a planned cross-cohort analysis of genetic variation in cardiovascular, pulmonary, hematologic, and sleep-related traits, comprises >40,000 participants representing 4 ethnic groups in 9 community-based cohorts. The goals of CARe include the discovery of new variants associated with traits using a candidate gene approach and the discovery of new variants using the genome-wide association mapping approach specifically in African Americans.

METHODS AND RESULTS: CARe has assembled DNA samples for >40,000 individuals self-identified as European American, African American, Hispanic, or Chinese American, with accompanying data on hundreds of phenotypes that have been standardized and deposited in the CARe Phenotype Database. All participants were genotyped for 7 single-nucleotide polymorphisms (SNPs) selected based on prior association evidence. We performed association analyses relating each of these SNPs to lipid traits, stratified by sex and ethnicity, and adjusted for age and age squared. In at least 2 of the ethnic groups, SNPs near CETP, LIPC, and LPL strongly replicated for association with high-density lipoprotein cholesterol concentrations, PCSK9 with low-density lipoprotein cholesterol levels, and LPL and APOA5 with serum triglycerides. Notably, some SNPs showed varying effect sizes and significance of association in different ethnic groups.

CONCLUSIONS: The CARe Pilot Study validates the operational framework for phenotype collection, SNP genotyping, and analytic pipeline of the CARe project and validates the planned candidate gene study of approximately 2000 biological candidate loci in all participants and genome-wide association study in approximately 8000 African American participants. CARe will serve as a valuable resource for the scientific community.

URLhttp://circgenetics.ahajournals.org/cgi/pmidlookup?view=long&pmid=20400780
DOI10.1161/CIRCGENETICS.109.882696
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/20400780?dopt=Abstract

Alternate JournalCirc Cardiovasc Genet
PubMed ID20400780
PubMed Central IDPMC3048024
Grant ListN01HC55020 / HL / NHLBI NIH HHS / United States
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N01-HC-25195 / HC / NHLBI NIH HHS / United States
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