2010-11-01
Genetic variants influencing circulating lipid levels and risk of coronary artery disease
Publication
Publication
Arteriosclerosis, Thrombosis, and Vascular Biology , Volume 30 - Issue 11 p. 2264- 2276
OBJECTIVE-: Genetic studies might provide new insights into the biological mechanisms underlying lipid metabolism and risk of CAD. We therefore conducted a genome-wide association study to identify novel genetic determinants of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides. METHODS AND RESULTS-: We combined genome-wide association data from 8 studies, comprising up to 17 723 participants with information on circulating lipid concentrations. We did independent replication studies in up to 37 774 participants from 8 populations and also in a population of Indian Asian descent. We also assessed the association between single-nucleotide polymorphisms (SNPs) at lipid loci and risk of CAD in up to 9 633 cases and 38 684 controls. We identified 4 novel genetic loci that showed reproducible associations with lipids (probability values, 1.6×10-8to 3.1×10-10). These include a potentially functional SNP in the SLC39A8 gene for HDL-C, an SNP near the MYLIP/GMPR and PPP1R3B genes for LDL-C, and at the AFF1 gene for triglycerides. SNPs showing strong statistical association with 1 or more lipid traits at the CELSR2, APOB, APOE-C1-C4-C2 cluster, LPL, ZNF259-APOA5-A4-C3-A1 cluster and TRIB1 loci were also associated with CAD risk (probability values, 1.1×10-3to 1.2×10-9). CONCLUSION-: We have identified 4 novel loci associated with circulating lipids. We also show that in addition to those that are largely associated with LDL-C, genetic loci mainly associated with circulating triglycerides and HDL-C are also associated with risk of CAD. These findings potentially provide new insights into the biological mechanisms underlying lipid metabolism and CAD risk.
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| doi.org/10.1161/ATVBAHA.109.201020, hdl.handle.net/1765/28251 | |
| Arteriosclerosis, Thrombosis, and Vascular Biology | |
| Organisation | Erasmus MC: University Medical Center Rotterdam |
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Waterworth, D., Ricketts, S., Song, K., Chen, L., Zhao, J. H., Ripatti, S., … Sandhu, M. (2010). Genetic variants influencing circulating lipid levels and risk of coronary artery disease. Arteriosclerosis, Thrombosis, and Vascular Biology, 30(11), 2264–2276. doi:10.1161/ATVBAHA.109.201020 |
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