Candidate Gene Association Resource (CARe): Design, methods, and proof of concept

Kiran Musunuru, Guillaume Lettre, Taylor Young, Deborah N. Farlow, James P. Pirruccello, Kenechi G. Ejebe, Brendan J. Keating, Qiong Yang, Ming Huei Chen, Nina Lapchyk, Andrew Crenshaw, Liuda Ziaugra, Anthony Rachupka, Emelia J. Benjamin, L. Adrienne Cupples, Myriam Fornage, Ervin R. Fox, Susan R. Heckbert, Joel N. Hirschhorn, Christopher Newton-ChehMarcia M. Nizzari, Dina N. Paltoo, George J. Papanicolaou, Sanjay R. Patel, Bruce M. Psaty, Daniel J. Rader, Susan Redline, Stephen S. Rich, Jerome I. Rotter, Herman A. Taylor, Russell P. Tracy, Ramachandran S. Vasan, James G. Wilson, Sekar Kathiresan, Richard R. Fabsitz, Eric Boerwinkle, Stacey B. Gabriel

Research output: Contribution to journalArticlepeer-review

124 Scopus citations


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 ≈2000 biological candidate loci in all participants and genome-wide association study in ≈8000 African American participants. CARe will serve as a valuable resource for the scientific community.

Original languageEnglish (US)
Pages (from-to)267-275
Number of pages9
JournalCirculation: Cardiovascular Genetics
Issue number3
StatePublished - Jun 2010
Externally publishedYes


  • Epidemiology
  • Genetics
  • Lipids

ASJC Scopus subject areas

  • Genetics
  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)


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