Genome-wide association study of Lp-PLA(2) activity and mass in the Framingham Heart Study.

Abstract

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.

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Citation

Published Version (Please cite this version)

10.1371/journal.pgen.1000928

Publication Info

Suchindran, Sunil, David Rivedal, John R Guyton, Tom Milledge, Xiaoyi Gao, Ashlee Benjamin, Jennifer Rowell, Geoffrey S Ginsburg, et al. (2010). Genome-wide association study of Lp-PLA(2) activity and mass in the Framingham Heart Study. PLoS Genet, 6(4). p. e1000928. 10.1371/journal.pgen.1000928 Retrieved from https://hdl.handle.net/10161/13543.

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Scholars@Duke

Rowell

Jennifer Voigt Rowell

Assistant Professor of Medicine
McCarthy

Jeanette Joan McCarthy

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 magazine in this field, Genome, where I served as editor-in-chief until 2016. I teach genomic and precision medicine online through Coursera and through the Precision Medicine Academy. I also design and deliver custom workshops and courses to international audiences. My workshops and online courses are meant to increase awareness, improve genomic literacy and teach practical skills for implementing precision medicine.  I am also coauthor of the book, Precision Medicine: A Guide to Genomics in Clinical Practice (2016, McGraw Hill Education).

Visit: Precision Medicine Academy  precisionmedicineacademy.org


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