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

dc.contributor.author Benjamin, Ashlee M
dc.contributor.author Gao, X
dc.contributor.author Ginsburg, Geoffrey Steven
dc.contributor.author Guyton, John Richard
dc.contributor.author McCarthy, Jeanette Joan
dc.contributor.author Milledge, Tom
dc.contributor.author Rivedal, D
dc.contributor.author Rowell, J
dc.contributor.author Suchindran, Sunil
dc.coverage.spatial United States
dc.date.accessioned 2011-06-21T17:31:17Z
dc.date.issued 2010-04-29
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/20442857
dc.identifier.uri http://hdl.handle.net/10161/4465
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.language eng
dc.language.iso en_US
dc.relation.ispartof PLoS Genet
dc.relation.isversionof 10.1371/journal.pgen.1000928
dc.relation.isreplacedby 10161/13543
dc.relation.isreplacedby http://hdl.handle.net/10161/13543
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
dc.description.version Version of Record
duke.date.pubdate 2010-4-0
duke.description.issue 4
duke.description.volume 6
dc.relation.journal Plos Genetics
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/20442857
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
dc.identifier.eissn 1553-7404


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