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Multiple Associated Variants Increase the Heritability Explained for Plasma Lipids and Coronary Artery Disease.
MedLine Citation:
PMID:  25170055     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND: -Plasma lipid levels as well as coronary artery disease (CAD) have been shown to be highly heritable with estimates ranging from 40%-60%. However, top variants detected by large-scale genome-wide association studies (GWAS) explain only a fraction of the total variance in plasma lipid phenotypes and CAD.
METHODS AND RESULTS: -We performed a conditional and joint association analysis using summary-level statistics from two large GWAS meta-analyses: (1) the Global Lipids Genetics Consortium (GLGC) study, and (2) the Coronary ARtery DIsease Genome-wide Replication and Meta-analysis (CARDIoGRAM) study. There were 100,184 individuals from 46 GLGC studies for plasma lipids, and 22,233 cases and 64,762 controls from 14 studies for CAD. We detected a number of loci where multiple independent SNPs were associated with lipid traits within a locus (12 out of 33 loci for high-density lipoprotein cholesterol [HDL-C], 10 of 35 loci for low-density lipoprotein cholesterol [LDL-C], 13 of 44 loci for total cholesterol [TC], and 8 of 28 loci for triglycerides [TG]), reaching genome-wide significance (P<5×10(-8)), nearly doubling the heritability explained by GWAS (3.6% to 7.6% for HDL-C, 5.0% to 8.8% for LDL-C, 5.5% to 8.8% for TC, and 5.7% to 8.5% for TG). Multiple SNPs were also associated with CAD (3 of 15 loci, 9.6% to 11.4% of increased heritability).
CONCLUSIONS: -These results demonstrate that a portion of the missing heritability for lipid traits and CAD can be explained by multiple variants at each locus.
Authors:
Hayato Tada; Hong-Hee Won; Olle Melander; Jian Yang; Gina M Peloso; Sekar Kathiresan
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-8-28
Journal Detail:
Title:  Circulation. Cardiovascular genetics     Volume:  -     ISSN:  1942-3268     ISO Abbreviation:  Circ Cardiovasc Genet     Publication Date:  2014 Aug 
Date Detail:
Created Date:  2014-8-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101489144     Medline TA:  Circ Cardiovasc Genet     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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