title: Candidate gene association resource (CARe): design, methods, and proof of concept.
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.
  
  
  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.
authors.affiliation: Broad Institute, Cambridge, MA 02142, USA.
authors.forename: Kiran
authors.initials: K
authors.lastname: Musunuru
authors.forename: Guillaume
authors.initials: G
authors.lastname: Lettre
authors.forename: Taylor
authors.initials: T
authors.lastname: Young
authors.forename: Deborah N
authors.initials: DN
authors.lastname: Farlow
authors.forename: James P
authors.initials: JP
authors.lastname: Pirruccello
authors.forename: Kenechi G
authors.initials: KG
authors.lastname: Ejebe
authors.forename: Brendan J
authors.initials: BJ
authors.lastname: Keating
authors.forename: Qiong
authors.initials: Q
authors.lastname: Yang
authors.forename: Ming-Huei
authors.initials: MH
authors.lastname: Chen
authors.forename: Nina
authors.initials: N
authors.lastname: Lapchyk
authors.forename: Andrew
authors.initials: A
authors.lastname: Crenshaw
authors.forename: Liuda
authors.initials: L
authors.lastname: Ziaugra
authors.forename: Anthony
authors.initials: A
authors.lastname: Rachupka
authors.forename: Emelia J
authors.initials: EJ
authors.lastname: Benjamin
authors.forename: L Adrienne
authors.initials: LA
authors.lastname: Cupples
authors.forename: Myriam
authors.initials: M
authors.lastname: Fornage
authors.forename: Ervin R
authors.initials: ER
authors.lastname: Fox
authors.forename: Susan R
authors.initials: SR
authors.lastname: Heckbert
authors.forename: Joel N
authors.initials: JN
authors.lastname: Hirschhorn
authors.forename: Christopher
authors.initials: C
authors.lastname: Newton-Cheh
authors.forename: Marcia M
authors.initials: MM
authors.lastname: Nizzari
authors.forename: Dina N
authors.initials: DN
authors.lastname: Paltoo
authors.forename: George J
authors.initials: GJ
authors.lastname: Papanicolaou
authors.forename: Sanjay R
authors.initials: SR
authors.lastname: Patel
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Psaty
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Rader
authors.forename: Susan
authors.initials: S
authors.lastname: Redline
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Rich
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.forename: Herman A
authors.initials: HA
authors.lastname: Taylor
authors.forename: Russell P
authors.initials: RP
authors.lastname: Tracy
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
authors.forename: James G
authors.initials: JG
authors.lastname: Wilson
authors.forename: Sekar
authors.initials: S
authors.lastname: Kathiresan
authors.forename: Richard R
authors.initials: RR
authors.lastname: Fabsitz
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.forename: Stacey B
authors.initials: SB
authors.lastname: Gabriel
mesh_terms: D001741:Black or African American / Q000235:genetics; D008076:Cholesterol, HDL / Q000097:blood / Q000235:genetics; D008078:Cholesterol, LDL / Q000097:blood / Q000235:genetics; D015331:Cohort Studies; D030541:Databases, Genetic; D056726:Genetic Association Studies / Q000379:methods*; D005838:Genotype; D006801:Humans; D010641:Phenotype; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide; D012107:Research Design; D014280:Triglycerides / Q000097:blood / Q000235:genetics; D044465:White People / Q000235:genetics
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides
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