Skip to main content

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

Publication ,  Journal Article
Suchindran, S; Rivedal, D; Guyton, JR; Milledge, T; Gao, X; Benjamin, A; Rowell, J; Ginsburg, GS; McCarthy, JJ
Published in: PLoS Genet
April 29, 2010

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.

Duke Scholars

Published In

PLoS Genet

DOI

EISSN

1553-7404

Publication Date

April 29, 2010

Volume

6

Issue

4

Start / End Page

e1000928

Location

United States

Related Subject Headings

  • Risk Factors
  • Polymorphism, Single Nucleotide
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Genome, Human
  • Genetic Predisposition to Disease
  • Developmental Biology
  • Cardiovascular Diseases
  • 3105 Genetics
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Suchindran, S., Rivedal, D., Guyton, J. R., Milledge, T., Gao, X., Benjamin, A., … McCarthy, J. J. (2010). Genome-wide association study of Lp-PLA(2) activity and mass in the Framingham Heart Study. PLoS Genet, 6(4), e1000928. https://doi.org/10.1371/journal.pgen.1000928
Suchindran, Sunil, David Rivedal, John R. Guyton, Tom Milledge, Xiaoyi Gao, Ashlee Benjamin, Jennifer Rowell, Geoffrey S. Ginsburg, and Jeanette J. McCarthy. “Genome-wide association study of Lp-PLA(2) activity and mass in the Framingham Heart Study.PLoS Genet 6, no. 4 (April 29, 2010): e1000928. https://doi.org/10.1371/journal.pgen.1000928.
Suchindran S, Rivedal D, Guyton JR, Milledge T, Gao X, Benjamin A, et al. Genome-wide association study of Lp-PLA(2) activity and mass in the Framingham Heart Study. PLoS Genet. 2010 Apr 29;6(4):e1000928.
Suchindran, Sunil, et al. “Genome-wide association study of Lp-PLA(2) activity and mass in the Framingham Heart Study.PLoS Genet, vol. 6, no. 4, Apr. 2010, p. e1000928. Pubmed, doi:10.1371/journal.pgen.1000928.
Suchindran S, Rivedal D, Guyton JR, Milledge T, Gao X, Benjamin A, Rowell J, Ginsburg GS, McCarthy JJ. Genome-wide association study of Lp-PLA(2) activity and mass in the Framingham Heart Study. PLoS Genet. 2010 Apr 29;6(4):e1000928.

Published In

PLoS Genet

DOI

EISSN

1553-7404

Publication Date

April 29, 2010

Volume

6

Issue

4

Start / End Page

e1000928

Location

United States

Related Subject Headings

  • Risk Factors
  • Polymorphism, Single Nucleotide
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Genome, Human
  • Genetic Predisposition to Disease
  • Developmental Biology
  • Cardiovascular Diseases
  • 3105 Genetics