Genome-wide association study of Lp-PLA(2) activity and mass in the Framingham Heart Study.
Journal Article (Journal Article)
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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Duke Authors
Cited Authors
- Suchindran, S; Rivedal, D; Guyton, JR; Milledge, T; Gao, X; Benjamin, A; Rowell, J; Ginsburg, GS; McCarthy, JJ
Published Date
- April 29, 2010
Published In
Volume / Issue
- 6 / 4
Start / End Page
- e1000928 -
PubMed ID
- 20442857
Pubmed Central ID
- PMC2861686
Electronic International Standard Serial Number (EISSN)
- 1553-7404
Digital Object Identifier (DOI)
- 10.1371/journal.pgen.1000928
Language
- eng
Conference Location
- United States