MedStar Authors catalog › Details for: Analysis of metabolic syndrome components in >15 000 african americans identifies pleiotropic variants: results from the population architecture using genomics and epidemiology study.
Analysis of metabolic syndrome components in >15 000 african americans identifies pleiotropic variants: results from the population architecture using genomics and epidemiology study. Journal: Circulation. Cardiovascular genetics. ISSN: 1942-3268. UI/PMID: 25023634. Subject(s): *African Americans/ge [Genetics] | Aged | Alleles | Apolipoprotein C-I/ge [Genetics] | Apolipoproteins A/ge [Genetics] | Blood Glucose/an [Analysis] | Cholesterol Ester Transfer Proteins/ge [Genetics] | Cholesterol, HDL/bl [Blood] | Female | Genetic Loci | Genetic Pleiotropy | Genetic Predisposition to Disease | Genetic Variation | *Genomics | Genotype | Hispanic Americans/ge [Genetics] | Humans | Lipoprotein Lipase/ge [Genetics] | Male | Metabolic Syndrome X/ep [Epidemiology] | *Metabolic Syndrome X/ge [Genetics] | Middle Aged | Odds Ratio | Phenotype | Polymorphism, Single Nucleotide | Transcription Factor 7-Like 2 Protein/ge [Genetics] Institution(s): MedStar Health Research Institute Activity type: Journal Article. Medline article type(s): Journal Article | Meta-Analysis | Research Support, N.I.H., Extramural | Research Support, Non-U.S. Gov't Online resources: Click here to access online Digital Object Identifier: http://dx.doi.org/10.1161/CIRCGENETICS.113.000386 (Click here) Abbreviated citation: Circ Cardiovasc Genet. 7(4):505-13, 2014 Aug. Abstract: BACKGROUND: Metabolic syndrome (MetS) refers to the clustering of cardiometabolic risk factors, including dyslipidemia, central adiposity, hypertension, and hyperglycemia, in individuals. Identification of pleiotropic genetic factors associated with MetS traits may shed light on key pathways or mediators underlying MetS. Abstract: METHODS AND RESULTS: Using the Metabochip array in 15 148 African Americans from the Population Architecture using Genomics and Epidemiology (PAGE) study, we identify susceptibility loci and investigate pleiotropy among genetic variants using a subset-based meta-analysis method, ASsociation-analysis-based-on-subSETs (ASSET). Unlike conventional models that lack power when associations for MetS components are null or have opposite effects, Association-analysis-based-on-subsets uses 1-sided tests to detect positive and negative associations for components separately and combines tests accounting for correlations among components. With Association-analysis-based-on-subsets, we identify 27 single nucleotide polymorphisms in 1 glucose and 4 lipids loci (TCF7L2, LPL, APOA5, CETP, and APOC1/APOE/TOMM40) significantly associated with MetS components overall, all P<2.5e-7, the Bonferroni adjusted P value. Three loci replicate in a Hispanic population, n=5172. A novel African American-specific variant, rs12721054/APOC1, and rs10096633/LPL are associated with >3 MetS components. We find additional evidence of pleiotropy for APOE, TOMM40, TCF7L2, and CETP variants, many with opposing effects (eg, the same rs7901695/TCF7L2 allele is associated with increased odds of high glucose and decreased odds of central adiposity).
Abstract: CONCLUSIONS: We highlight a method to increase power in large-scale genomic association analyses and report a novel variant associated with all MetS components in African Americans. We also identify pleiotropic associations that may be clinically useful in patient risk profiling and for informing translational research of potential gene targets and medications.Copyright � 2014 American Heart Association, Inc.