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A phenomics-based strategy identifies loci on APOC1, BRAP, and PLCG1 associated with metabolic syndrome phenotype domains.
Tuesday,2012-11-06 12:26 America/Los_Angeles — eenright
| Title | A phenomics-based strategy identifies loci on APOC1, BRAP, and PLCG1 associated with metabolic syndrome phenotype domains. |
| Publication Type | Journal Article |
| Year of Publication | 2011 |
| Authors | Avery, CL, He, Q, North, KE, Ambite, JL, Boerwinkle, E, Fornage, M, Hindorff, LA, Kooperberg, C, Meigs, JB, Pankow, JS, Pendergrass, SA, Psaty, BM, Ritchie, MD, Rotter, JI, Taylor, KD, Wilkens, LR, Heiss, G, Lin, DYu |
| Journal | PLoS Genet |
| Volume | 7 |
| Issue | 10 |
| Pagination | e1002322 |
| Date Published | 2011 Oct |
| ISSN | 1553-7404 |
| Keywords | African Americans, Apolipoprotein C-I, Blood Glucose, Dyslipidemias, European Continental Ancestry Group, Genetic Association Studies, Genetic Predisposition to Disease, Genome, Human, Humans, Metabolic Syndrome, Obesity, Abdominal, Phenotype, Phospholipase C gamma, Polymorphism, Single Nucleotide, Quantitative Trait, Heritable, Ubiquitin-Protein Ligases, Vascular Diseases |
| Abstract | <p>Despite evidence of the clustering of metabolic syndrome components, current approaches for identifying unifying genetic mechanisms typically evaluate clinical categories that do not provide adequate etiological information. Here, we used data from 19,486 European American and 6,287 African American Candidate Gene Association Resource Consortium participants to identify loci associated with the clustering of metabolic phenotypes. Six phenotype domains (atherogenic dyslipidemia, vascular dysfunction, vascular inflammation, pro-thrombotic state, central obesity, and elevated plasma glucose) encompassing 19 quantitative traits were examined. Principal components analysis was used to reduce the dimension of each domain such that >55% of the trait variance was represented within each domain. We then applied a statistically efficient and computational feasible multivariate approach that related eight principal components from the six domains to 250,000 imputed SNPs using an additive genetic model and including demographic covariates. In European Americans, we identified 606 genome-wide significant SNPs representing 19 loci. Many of these loci were associated with only one trait domain, were consistent with results in African Americans, and overlapped with published findings, for instance central obesity and FTO. However, our approach, which is applicable to any set of interval scale traits that is heritable and exhibits evidence of phenotypic clustering, identified three new loci in or near APOC1, BRAP, and PLCG1, which were associated with multiple phenotype domains. These pleiotropic loci may help characterize metabolic dysregulation and identify targets for intervention.</p> |
| DOI | 10.1371/journal.pgen.1002322 |
| Alternate Journal | PLoS Genet. |
| PubMed ID | 22022282 |
| PubMed Central ID | PMC3192835 |
| Grant List | N01HC55020 / HL / NHLBI NIH HHS / United States R01 DK078616 / DK / NIDDK NIH HHS / United States P30 ES010126 / ES / NIEHS NIH HHS / United States U01CA98758 / CA / NCI NIH HHS / United States N01HC95160 / HL / NHLBI NIH HHS / United States N01HC95163 / HL / NHLBI NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States U01 HG004790 / HG / NHGRI NIH HHS / United States N01HC48049 / HL / NHLBI NIH HHS / United States U01 HG004802 / HG / NHGRI NIH HHS / United States U01 HG007416 / HG / NHGRI NIH HHS / United States N01HC45205 / HL / NHLBI NIH HHS / United States N01 HC015103 / HC / NHLBI NIH HHS / United States N01HC95169 / HL / NHLBI NIH HHS / United States K99 HL098458 / HL / NHLBI NIH HHS / United States N01 HC085085 / HC / NHLBI NIH HHS / United States U01CA136792 / CA / NCI NIH HHS / United States N01HC95164 / HL / NHLBI NIH HHS / United States N01HC55222 / HL / 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 N01HC95168 / HL / NHLBI NIH HHS / United States N01HC95095 / HL / NHLBI NIH HHS / United States U01 HG004803 / HG / NHGRI NIH HHS / United States N01HC95165 / HL / NHLBI NIH HHS / United States N01HC95159 / HL / NHLBI NIH HHS / United States P01 CA033619 / CA / NCI NIH HHS / United States K24 DK080140 / DK / NIDDK NIH HHS / United States N01HC95161 / HL / NHLBI NIH HHS / United States N01 HC045134 / HC / NHLBI NIH HHS / United States N01HC55016 / HL / NHLBI NIH HHS / United States N01HC65226 / HL / 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 R37CA54281 / CA / NCI NIH HHS / United States N01HC48047 / HL / NHLBI NIH HHS / United States U01 CA098758 / CA / NCI NIH HHS / United States N01HC85083 / HL / NHLBI NIH HHS / United States N01HC25195 / HL / NHLBI NIH HHS / United States K99-HL-098458 / HL / NHLBI NIH HHS / United States U01 HG004798 / HG / NHGRI NIH HHS / United States N01HC45204 / HL / NHLBI NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States N01HC95166 / HL / NHLBI NIH HHS / United States N01HC55021 / HL / NHLBI NIH HHS / United States N01 HC045133 / HC / NHLBI NIH HHS / United States U01 CA136792 / CA / NCI NIH HHS / United States N01HC85080 / HL / NHLBI NIH HHS / United States R37 CA054281 / CA / NCI NIH HHS / United States N01 HC035129 / HC / NHLBI NIH HHS / United States N01WH22110 / WH / WHI NIH HHS / United States P01CA33619 / CA / NCI NIH HHS / United States N01HC48048 / HL / NHLBI NIH HHS / United States N01HC85081 / HL / NHLBI NIH HHS / United States |