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

Circ Cardiovasc Genet
Authors
Keywords
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.

Year of Publication
2010
Journal
Circ Cardiovasc Genet
Volume
3
Issue
3
Pages
267-75
Date Published
2010 Jun
ISSN
1942-3268
URL
DOI
10.1161/CIRCGENETICS.109.882696
PubMed ID
20400780
PubMed Central ID
PMC3048024
Links
Grant list
N01HC55020 / HL / NHLBI NIH HHS / United States
N01-HB-72992 / HB / NHLBI NIH HHS / United States
N01-HC-25195 / HC / NHLBI NIH HHS / United States
N01-HB-97068 / HB / NHLBI NIH HHS / United States
R01-HL-076784 / HL / NHLBI NIH HHS / United States
N01-HB-97053 / HB / NHLBI NIH HHS / United States
N01-HB-72997 / HB / NHLBI NIH HHS / United States
N01-HB-73003 / HB / NHLBI NIH HHS / United States
N01-HC-45205 / HC / NHLBI NIH HHS / United States
N01-HC-95162 / HC / NHLBI NIH HHS / United States
U01-HL-063429 / HL / NHLBI NIH HHS / United States
N01-HC-05187 / HC / NHLBI NIH HHS / United States
N01HC95160 / HL / NHLBI NIH HHS / United States
U01-HL-053916 / HL / NHLBI NIH HHS / United States
U01 HL053916 / HL / NHLBI NIH HHS / United States
N01HC55018 / HL / NHLBI NIH HHS / United States
R01 HL046380 / HL / NHLBI NIH HHS / United States
N01HC95163 / HL / NHLBI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
N01-HC-48047 / HC / NHLBI NIH HHS / United States
U01 HL063463 / HL / NHLBI NIH HHS / United States
N01-HB-97064 / HB / NHLBI NIH HHS / United States
N01HC48049 / HL / NHLBI NIH HHS / United States
N01-HC-55022 / HC / NHLBI NIH HHS / United States
R01 HL092577 / HL / NHLBI NIH HHS / United States
N01-HC-85081 / HC / NHLBI NIH HHS / United States
N01HC45205 / HL / NHLBI NIH HHS / United States
N01-HC-95163 / HC / NHLBI NIH HHS / United States
N01 HC015103 / HC / NHLBI NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
N01-HC-95168 / HC / NHLBI NIH HHS / United States
N01HC95169 / HL / NHLBI NIH HHS / United States
N01-HB-73002 / HB / NHLBI NIH HHS / United States
N01-HC-45204 / HC / NHLBI NIH HHS / United States
N01-HB-72993 / HB / NHLBI NIH HHS / United States
N01 HC065226 / HC / NHLBI NIH HHS / United States
N01-HB-97070 / HB / NHLBI NIH HHS / United States
N01-HB-97056 / HB / NHLBI NIH HHS / United States
N01-HB-72982 / HB / NHLBI NIH HHS / United States
U01-HL-053934 / HL / NHLBI NIH HHS / United States
N01 HC085085 / HC / NHLBI NIH HHS / United States
N01-HB-73000 / HB / NHLBI NIH HHS / United States
N01-HC-95159 / HC / NHLBI NIH HHS / United States
U01-HL-080295 / HL / NHLBI NIH HHS / United States
R01 HL076784 / HL / NHLBI NIH HHS / United States
N01-HC-95095 / HC / NHLBI NIH HHS / United States
N01HC55022 / HL / NHLBI NIH HHS / United States
N01-HC-95165 / HC / NHLBI NIH HHS / United States
N01HC95164 / HL / NHLBI NIH HHS / United States
U01-HL-077813 / HL / NHLBI NIH HHS / United States
N01-HB-97085 / HB / NHLBI NIH HHS / United States
U01-HL-064360 / HL / NHLBI NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
N01-HC-55021 / HC / NHLBI NIH HHS / United States
U01 HL053938 / HL / NHLBI NIH HHS / United States
R01-AG-028321 / AG / NIA NIH HHS / United States
N01-HC-85086 / HC / NHLBI NIH HHS / United States
N01HC55015 / HL / NHLBI NIH HHS / United States
N01HC95162 / HL / NHLBI NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
N01-HB-73005 / HB / NHLBI NIH HHS / United States
N01-HC-48050 / HC / NHLBI NIH HHS / United States
N01HC95168 / HL / NHLBI NIH HHS / United States
U01 HL064360 / HL / NHLBI NIH HHS / United States
M01-RR-00080 / RR / NCRR NIH HHS / United States
N01-HC-85082 / HC / NHLBI NIH HHS / United States
N01-HB-73006 / HB / NHLBI NIH HHS / United States
N01HC95170 / HL / NHLBI NIH HHS / United States
N01-HC-55019 / HC / NHLBI NIH HHS / United States
U01 HL077813 / HL / NHLBI NIH HHS / United States
U01-HL-063463 / HL / NHLBI NIH HHS / United States
N01HC95095 / HL / NHLBI NIH HHS / United States
N01-HB-97071 / HB / NHLBI NIH HHS / United States
N01-HB-97066 / HB / NHLBI NIH HHS / United States
N01-HC-55015 / HC / NHLBI NIH HHS / United States
U01 HL053941 / HL / NHLBI NIH HHS / United States
N01-HC-95169 / HC / NHLBI NIH HHS / United States
N01-HB-7300 / HB / NHLBI NIH HHS / United States
N01-HC-95164 / HC / NHLBI NIH HHS / United States
N01HC95165 / HL / NHLBI NIH HHS / United States
N01-HB-72995 / HB / NHLBI NIH HHS / United States
N01HC95159 / HL / NHLBI NIH HHS / United States
N01-HC-55222 / HC / NHLBI NIH HHS / United States
R01-HL-071205 / HL / NHLBI NIH HHS / United States
N01-HB-97062 / HB / NHLBI NIH HHS / United States
N01-HC-48049 / HC / NHLBI NIH HHS / United States
N01-HB-97051 / HB / NHLBI NIH HHS / United States
N01-HC-85083 / HC / NHLBI NIH HHS / United States
N01HC95161 / HL / NHLBI NIH HHS / United States
N01-HC-75150 / HC / NHLBI NIH HHS / United States
N01 HC045134 / HC / NHLBI NIH HHS / United States
N01-HC-55020 / HC / NHLBI NIH HHS / United States
N01-HB-73001 / HB / NHLBI NIH HHS / United States
N01-HC-85080 / HC / NHLBI NIH HHS / United States
N01-HB-97060 / HB / NHLBI NIH HHS / United States
N01-HC-95160 / HC / NHLBI NIH HHS / United States
N01HC55016 / HL / NHLBI NIH HHS / United States
N01HC65226 / HL / NHLBI NIH HHS / United States
R01-HL-46380 / HL / NHLBI NIH HHS / United States
N01-HC-95171 / HC / NHLBI NIH HHS / United States
U01-HL-053937 / HL / NHLBI NIH HHS / United States
N01-HB-97073 / HB / NHLBI NIH HHS / United States
N01-HB-97054 / HB / NHLBI NIH HHS / United States
U01 HL053934 / HL / NHLBI NIH HHS / United States
U01 HL063429 / HL / NHLBI NIH HHS / United States
N01-HB-72994 / HB / NHLBI NIH HHS / United States
N01 HC085084 / HC / NHLBI NIH HHS / United States
N01HC48050 / HL / NHLBI NIH HHS / United States
N01HC55019 / HL / NHLBI NIH HHS / United States
N01HC85082 / HL / NHLBI NIH HHS / United States
N01HC75150 / HL / NHLBI NIH HHS / United States
N01HC05187 / HL / NHLBI NIH HHS / United States
N01HC95167 / HL / NHLBI NIH HHS / United States
N01-HC-95172 / HC / NHLBI NIH HHS / United States
N01HC48047 / HL / NHLBI NIH HHS / United States
N01HC85083 / HL / NHLBI NIH HHS / United States
N01HC95171 / HL / NHLBI NIH HHS / United States
N01HC25195 / HL / NHLBI NIH HHS / United States
R01 HL071205 / HL / NHLBI NIH HHS / United States
N01-HB-72991 / HB / NHLBI NIH HHS / United States
N01-HB-97072 / HB / NHLBI NIH HHS / United States
N01-HC-85079 / HC / NHLBI NIH HHS / United States
N01-HC-95161 / HC / NHLBI NIH HHS / United States
N01-HC-95100 / HC / NHLBI NIH HHS / United States
N01HC45204 / HL / NHLBI NIH HHS / United States
N01-HB-97058 / HB / NHLBI NIH HHS / United States
U01-HL-053941 / HL / NHLBI NIH HHS / United States
U01 HL053937 / HL / NHLBI NIH HHS / United States
N01-HC-48048 / HC / NHLBI NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
N01HC95166 / HL / NHLBI NIH HHS / United States
N01-HB-72996 / HB / NHLBI NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States
N01HC55021 / HL / NHLBI NIH HHS / United States
R01 AG028321 / AG / NIA NIH HHS / United States
N01-HC-95166 / HC / NHLBI NIH HHS / United States
N01-HB-97061 / HB / NHLBI NIH HHS / United States
R01-HL-092577 / HL / NHLBI NIH HHS / United States
M01 RR000080 / RR / NCRR NIH HHS / United States
N01HC85080 / HL / NHLBI NIH HHS / United States
N01-HC-95170 / HC / NHLBI NIH HHS / United States
N01-HB-72998 / HB / NHLBI NIH HHS / United States
N01 HC035129 / HC / NHLBI NIH HHS / United States
N01-HB-97069 / HB / NHLBI NIH HHS / United States
N01HC48048 / HL / NHLBI NIH HHS / United States
N01-HC-95167 / HC / NHLBI NIH HHS / United States
N01HC85081 / HL / NHLBI NIH HHS / United States
N01-HC-65226 / HC / NHLBI NIH HHS / United States
N01HC95172 / HL / NHLBI NIH HHS / United States