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Evaluation of the metabochip genotyping array in African Americans and implications for fine mapping of GWAS-identified loci: the PAGE study.
Monday,2015-03-09 16:31 America/Los_Angeles — zdrager
| Title | Evaluation of the metabochip genotyping array in African Americans and implications for fine mapping of GWAS-identified loci: the PAGE study. |
| Publication Type | Journal Article |
| Year of Publication | 2012 |
| Authors | Buyske, S, Wu, Y, Carty, CL, Cheng, I, Assimes, TL, Dumitrescu, L, Hindorff, LA, Mitchell, S, Ambite, JLuis, Boerwinkle, E, Bůzková, P, Carlson, CS, Cochran, B, Duggan, D, Eaton, CB, Fesinmeyer, MD, Franceschini, N, Haessler, J, Jenny, N, Kang, HMin, Kooperberg, C, Lin, Y, Le Marchand, L, Matise, TC, Robinson, JG, Rodriguez, C, Schumacher, FR, Voight, BF, Young, A, Manolio, TA, Mohlke, KL, Haiman, CA, Peters, U, Crawford, DC, North, KE |
| Journal | PLoS One |
| Volume | 7 |
| Issue | 4 |
| Pagination | e35651 |
| Date Published | 2012 |
| ISSN | 1932-6203 |
| Keywords | African Americans, Cardiovascular Diseases, Cholesterol Ester Transfer Proteins, Cholesterol, HDL, Cholesterol, LDL, Chromosomes, Human, Cohort Studies, Gene Frequency, Genome-Wide Association Study, Genotype, Humans, Metabolic Diseases, Polymorphism, Single Nucleotide, Quantitative Trait Loci |
| Abstract | <p>The Metabochip is a custom genotyping array designed for replication and fine mapping of metabolic, cardiovascular, and anthropometric trait loci and includes low frequency variation content identified from the 1000 Genomes Project. It has 196,725 SNPs concentrated in 257 genomic regions. We evaluated the Metabochip in 5,863 African Americans; 89% of all SNPs passed rigorous quality control with a call rate of 99.9%. Two examples illustrate the value of fine mapping with the Metabochip in African-ancestry populations. At CELSR2/PSRC1/SORT1, we found the strongest associated SNP for LDL-C to be rs12740374 (p = 3.5 × 10(-11)), a SNP indistinguishable from multiple SNPs in European ancestry samples due to high correlation. Its distinct signal supports functional studies elsewhere suggesting a causal role in LDL-C. At CETP we found rs17231520, with risk allele frequency 0.07 in African Americans, to be associated with HDL-C (p = 7.2 × 10(-36)). This variant is very rare in Europeans and not tagged in common GWAS arrays, but was identified as associated with HDL-C in African Americans in a single-gene study. Our results, one narrowing the risk interval and the other revealing an associated variant not found in Europeans, demonstrate the advantages of high-density genotyping of common and rare variation for fine mapping of trait loci in African American samples.</p> |
| DOI | 10.1371/journal.pone.0035651 |
| Alternate Journal | PLoS ONE |
| PubMed ID | 22539988 |
| PubMed Central ID | PMC3335090 |
| Grant List | 24152 / / PHS HHS / United States 32100-2 / / PHS HHS / United States 32105-6 / / PHS HHS / United States 32108-9 / / PHS HHS / United States 32111-13 / / PHS HHS / United States 32115 / / PHS HHS / United States 32118-32119 / / PHS HHS / United States 32122 / / PHS HHS / United States 42107-26 / / PHS HHS / United States 42129-32 / / PHS HHS / United States 44221 / / PHS HHS / United States N01-HC-55015 / HC / NHLBI NIH HHS / United States N01-HC-55016 / HC / NHLBI NIH HHS / United States N01-HC-55018 / HC / NHLBI NIH HHS / United States N01-HC-55019 / HC / NHLBI NIH HHS / United States N01-HC-55020 / HC / NHLBI NIH HHS / United States N01-HC-55021 / HC / NHLBI NIH HHS / United States N01-HC-55022 / HC / NHLBI NIH HHS / United States N01WH22110 / WH / WHI NIH HHS / United States P01CA33619 / CA / NCI NIH HHS / United States P30 CA015704 / CA / NCI NIH HHS / United States R01 HL104199 / HL / NHLBI NIH HHS / United States R37CA54281 / CA / NCI NIH HHS / United States U01 HG004790 / HG / NHGRI NIH HHS / United States U01CA136792 / CA / NCI NIH HHS / United States U01CA98758 / CA / NCI NIH HHS / United States U01HG004790 / HG / NHGRI NIH HHS / United States U01HG004798 / HG / NHGRI NIH HHS / United States U01HG004801 / HG / NHGRI NIH HHS / United States U01HG004802 / HG / NHGRI NIH HHS / United States U01HG004803 / HG / NHGRI NIH HHS / United States |