1. Newly identified loci that influence lipid concentrations and risk of coronary artery disease
- Author
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Richard N. Bergman, Derrick A Bennett, Cristen J. Willer, Richard M. Watanabe, Nicholas J. Timpson, Karen L. Mohlke, Robert Clarke, Francis S. Collins, Laura J. Scott, Antonio Cao, Angelo Scuteri, Alan R. Shuldiner, Antonella Mulas, G. Mark Lathrop, Andrea Maschio, Samer S. Najjar, Diana Zelenika, Serena Sanna, William L. Duren, Michael Boehnke, Jaakko Tuomilehto, Pilar Galan, James B. Strait, Heather M. Stringham, Debbie A Lawlor, Rory Collins, Ramaiah Nagaraja, Anne U. Jackson, Yun Li, Jouko Sundvall, Sarah Parish, Manuela Uda, George Davey-Smith, Giuseppe Albai, Paul Scheet, Shah Ebrahim, Haiqing Shen, David Schlessinger, Pierre Meneton, Lori L. Bonnycastle, Simon Heath, Gonçalo R. Abecasis, Mario A. Morken, Wei-Min Chen, Edward G. Lakatta, Amy J. Swift, Yoav Ben-Shlomo, Narisu Narisu, Fabio Busonero, and Serge Hercberg
- Subjects
medicine.medical_specialty ,Apolipoprotein B ,Coronary Artery Disease ,030204 cardiovascular system & hematology ,Polymorphism, Single Nucleotide ,Article ,Cohort Studies ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Gene Frequency ,Risk Factors ,Internal medicine ,Genetics ,medicine ,Humans ,Computer Simulation ,Allele frequency ,Alleles ,Triglycerides ,030304 developmental biology ,Probability ,0303 health sciences ,Likelihood Functions ,biology ,Cholesterol ,Genome, Human ,PCSK9 ,Haplotype ,Cholesterol, HDL ,Genetic Variation ,Cholesterol, LDL ,Lipids ,Markov Chains ,3. Good health ,Endocrinology ,chemistry ,Haplotypes ,ABCA1 ,Case-Control Studies ,LDL receptor ,biology.protein ,lipids (amino acids, peptides, and proteins) ,Lipoprotein - Abstract
To identify genetic variants influencing plasma lipid concentrations, we first used genotype imputation and meta-analysis to combine three genome-wide scans totaling 8,816 individuals and comprising 6,068 individuals specific to our study (1,874 individuals from the FUSION study of type 2 diabetes and 4,184 individuals from the SardiNIA study of aging-associated variables) and 2,758 individuals from the Diabetes Genetics Initiative, reported in a companion study in this issue. We subsequently examined promising signals in 11,569 additional individuals. Overall, we identify strongly associated variants in eleven loci previously implicated in lipid metabolism (ABCA1, the APOA5-APOA4-APOC3-APOA1 and APOE-APOC clusters, APOB, CETP, GCKR, LDLR, LPL, LIPC, LIPG and PCSK9) and also in several newly identified loci (near MVK-MMAB and GALNT2, with variants primarily associated with high-density lipoprotein (HDL) cholesterol; near SORT1, with variants primarily associated with low-density lipoprotein (LDL) cholesterol; near TRIB1, MLXIPL and ANGPTL3, with variants primarily associated with triglycerides; and a locus encompassing several genes near NCAN, with variants strongly associated with both triglycerides and LDL cholesterol). Notably, the 11 independent variants associated with increased LDL cholesterol concentrations in our study also showed increased frequency in a sample of coronary artery disease cases versus controls.
- Published
- 2007