A Phenomics-Based Strategy Identifies Loci on APOC1, BRAP, and PLCG1 Associated with Metabolic Syndrome Phenotype Domains

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Citation

Avery, Christy L.; He, Qianchuan; North, Kari E.; Ambite, Jose Luis; Boerwinkle, Eric A.; Fornage, Myriam; Hindorff, Lucia A.; Kooperberg, Charles L.; Meigs, James B.; & Pankow, James S., et al. (2011). A Phenomics-Based Strategy Identifies Loci on APOC1, BRAP, and PLCG1 Associated with Metabolic Syndrome Phenotype Domains. PLOS Genetics, 7(10), e1002322. PMCID: PMC3192835

Abstract

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

URL

http://dx.doi.org/10.1371/journal.pgen.1002322

Reference Type

Journal Article

Year Published

2011

Journal Title

PLOS Genetics

Author(s)

Avery, Christy L.
He, Qianchuan
North, Kari E.
Ambite, Jose Luis
Boerwinkle, Eric A.
Fornage, Myriam
Hindorff, Lucia A.
Kooperberg, Charles L.
Meigs, James B.
Pankow, James S.
Pendergrass, Sarah A.
Psaty, Bruce M.
Ritchie, Marylyn D.
Rotter, Jerome I.
Taylor, Kent D.
Wilkens, Lynne R.
Heiss, Gerardo M.
Lin, Dan-Yu

PMCID

PMC3192835

ORCiD

Avery - 0000-0002-1044-8162