Genome-wide association study of Lp-PLA(2) activity and mass in the Framingham Heart Study.
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Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is an emerging risk factor and therapeutic target for cardiovascular disease. The activity and mass of this enzyme are heritable traits, but major genetic determinants have not been explored in a systematic, genome-wide fashion. We carried out a genome-wide association study of Lp-PLA(2) activity and mass in 6,668 Caucasian subjects from the population-based Framingham Heart Study. Clinical data and genotypes from the Affymetrix 550K SNP array were obtained from the open-access Framingham SHARe project. Each polymorphism that passed quality control was tested for associations with Lp-PLA(2) activity and mass using linear mixed models implemented in the R statistical package, accounting for familial correlations, and controlling for age, sex, smoking, lipid-lowering-medication use, and cohort. For Lp-PLA(2) activity, polymorphisms at four independent loci reached genome-wide significance, including the APOE/APOC1 region on chromosome 19 (p = 6 x 10(-24)); CELSR2/PSRC1 on chromosome 1 (p = 3 x 10(-15)); SCARB1 on chromosome 12 (p = 1x10(-8)) and ZNF259/BUD13 in the APOA5/APOA1 gene region on chromosome 11 (p = 4 x 10(-8)). All of these remained significant after accounting for associations with LDL cholesterol, HDL cholesterol, or triglycerides. For Lp-PLA(2) mass, 12 SNPs achieved genome-wide significance, all clustering in a region on chromosome 6p12.3 near the PLA2G7 gene. Our analyses demonstrate that genetic polymorphisms may contribute to inter-individual variation in Lp-PLA(2) activity and mass.
Genetic Predisposition to Disease
Genome-Wide Association Study
Polymorphism, Single Nucleotide
Published Version (Please cite this version)10.1371/journal.pgen.1000928
Publication InfoBenjamin, Ashlee M; Gao, X; Ginsburg, Geoffrey Steven; Guyton, John Richard; McCarthy, Jeanette Joan; Milledge, Tom; ... Suchindran, Sunil (2010). Genome-wide association study of Lp-PLA(2) activity and mass in the Framingham Heart Study. PLoS Genet, 6(4). pp. e1000928. 10.1371/journal.pgen.1000928. Retrieved from https://hdl.handle.net/10161/4465.
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Professor of Medicine
Dr. Geoffrey S. Ginsburg's research interests are in the development of novel paradigms for developing and translating genomic information into medical practice and the integration of personalized medicine into health care.
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Adjunct Associate Professor in the Department of Family Medicine and Community Health
As a genetic epidemiologist, I spent the earlier part of my career researching the genetic underpinnings of complex diseases, both infectious and chronic. More recently, I have turned my attention to precision medicine education. As a leading educator in the field of genomic and precision medicine, I now spend my time demystifying genomics for non-technical audiences, including health care providers, patients and other stakeholders. In 2014 I helped launch the first consumer-facing mag
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I work in Omic and biomarker research at the Center for Applied Genomics and Precision Medicine at Duke University. My current work focuses on infectious disease and cardiovascular disease. I have also worked on cardiovascular risk prediction, classification, and genome-wide association studies. Some of my work uses risk-prediction models and classification in Omic and other settings, and I give workshops on this topic and others. I am interested in any research that s
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