Genome-wide association study of Lp-PLA(2) activity and mass in the Framingham Heart Study.
| dc.contributor.author | Suchindran, Sunil | |
| dc.contributor.author | Rivedal, David | |
| dc.contributor.author | Guyton, John R | |
| dc.contributor.author | Milledge, Tom | |
| dc.contributor.author | Gao, Xiaoyi | |
| dc.contributor.author | Benjamin, Ashlee | |
| dc.contributor.author | Rowell, Jennifer | |
| dc.contributor.author | Ginsburg, Geoffrey S | |
| dc.contributor.author | McCarthy, Jeanette J | |
| dc.contributor.editor | McCarthy, Mark I | |
| dc.coverage.spatial | United States | |
| dc.date.accessioned | 2011-06-21T17:31:17Z | |
| dc.date.accessioned | 2017-02-01T14:30:46Z | |
| dc.date.issued | 2010-04-29 | |
| dc.description.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. | |
| dc.description.version | Version of Record | |
| dc.identifier | ||
| dc.identifier.eissn | 1553-7404 | |
| dc.identifier.uri | ||
| dc.language | eng | |
| dc.language.iso | en_US | |
| dc.publisher | Public Library of Science (PLoS) | |
| dc.relation.ispartof | PLoS Genet | |
| dc.relation.isversionof | 10.1371/journal.pgen.1000928 | |
| dc.relation.journal | Plos Genetics | |
| dc.relation.replaces | ||
| dc.relation.replaces | 10161/4465 | |
| dc.subject | 1-Alkyl-2-acetylglycerophosphocholine Esterase | |
| dc.subject | Cardiovascular Diseases | |
| dc.subject | Genetic Predisposition to Disease | |
| dc.subject | Genome, Human | |
| dc.subject | Genome-Wide Association Study | |
| dc.subject | Genotype | |
| dc.subject | Humans | |
| dc.subject | Polymorphism, Single Nucleotide | |
| dc.subject | Risk Factors | |
| dc.title | Genome-wide association study of Lp-PLA(2) activity and mass in the Framingham Heart Study. | |
| dc.title.alternative | ||
| dc.type | Journal article | |
| duke.contributor.orcid | Ginsburg, Geoffrey S|0000-0003-4739-9808 | |
| duke.date.pubdate | 2010-4-0 | |
| duke.description.issue | 4 | |
| duke.description.volume | 6 | |
| pubs.author-url | ||
| pubs.begin-page | e1000928 | |
| pubs.issue | 4 | |
| pubs.organisational-group | Biomedical Engineering | |
| pubs.organisational-group | Clinical Science Departments | |
| pubs.organisational-group | Community and Family Medicine | |
| pubs.organisational-group | Duke | |
| pubs.organisational-group | Duke Cancer Institute | |
| pubs.organisational-group | Institutes and Centers | |
| pubs.organisational-group | Medicine | |
| pubs.organisational-group | Medicine, Cardiology | |
| pubs.organisational-group | Medicine, Endocrinology, Metabolism, and Nutrition | |
| pubs.organisational-group | Pathology | |
| pubs.organisational-group | Pratt School of Engineering | |
| pubs.organisational-group | School of Medicine | |
| pubs.organisational-group | School of Nursing | |
| pubs.organisational-group | School of Nursing - Secondary Group | |
| pubs.publication-status | Published online | |
| pubs.volume | 6 |