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Candidate gene association resource (CARe): design, methods, and proof of concept.
Tuesday,2012-11-06 12:19 America/Los_Angeles — eenright
| Title | Candidate gene association resource (CARe): design, methods, and proof of concept. |
| Publication Type | Journal Article |
| Year of Publication | 2010 |
| Authors | Musunuru, 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, Cupples, AL, 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/Institutional Authors | NHLBI Candidate Gene Association Resource, |
| Journal | Circ Cardiovasc Genet |
| Volume | 3 |
| Issue | 3 |
| Pagination | 267-75 |
| Date Published | 2010 Jun |
| ISSN | 1942-3268 |
| Keywords | African 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 | <p><b>BACKGROUND: </b>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.</p><p><b>METHODS AND RESULTS: </b>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.</p><p><b>CONCLUSIONS: </b>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.</p> |
| DOI | 10.1161/CIRCGENETICS.109.882696 |
| Alternate Journal | Circ Cardiovasc Genet |
| PubMed ID | 20400780 |
| PubMed Central ID | PMC3048024 |
| 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 / 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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 T32 HL007208 / HL / NHLBI 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 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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 |