Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms
Copyright policy )Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms
Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P < 5 × 10(-8), in fixed-effects meta-analysis) from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leukocyte migration and atherosclerosis (PECAM1, rs1867624), coagulation and inflammation (PROCR, rs867186 (p.Ser219Gly)) and vascular smooth muscle cell differentiation (LMOD1, rs2820315). Correlation of these regions with cell-type-specific gene expression and plasma protein levels sheds light on potential disease mechanisms.
Male, Aging, 3102 Bioinformatics and computational biology (for-2020), Vascular (mesh), 3001 Agricultural biotechnology (for-2020), Energy Metabolism (mesh), Coronary Artery Disease, Cardiovascular, 11 Medical and Health Sciences (for), Medical and Health Sciences, 3105 Genetics (for-2020), Muscle, Smooth, Vascular, Aging (rcdc), Clinical Research (rcdc), Risk Factors, 2.1 Biological and endogenous factors, Male (mesh), Genetic Predisposition to Disease (mesh), Histone Code (mesh), EPIC-CVD, Developmental Biology (science-metrix), Coronary Artery Disease (mesh), Humans (mesh), Chemotaxis, Single Nucleotide, Arteries, Biological Sciences, Bioinformatics and computational biology, 06 Biological Sciences (for), Histone Code, Chemotaxis, Leukocyte, Heart Disease, Muscle, Cardiovascular (rcdc), Genome-Wide Association Study (mesh), Female, Smooth, Quantitative Trait Loci (mesh), Single Nucleotide (mesh), Genotype, Agricultural biotechnology, Quantitative Trait Loci, Heart Disease (rcdc), 610, Heart Disease - Coronary Heart Disease (rcdc), Polymorphism, Single Nucleotide, Arteries (mesh), Clinical Research, Risk Factors (mesh), Vascular, Genetics, Journal Article, Cell Adhesion, Humans, Genetic Predisposition to Disease, Polymorphism, Atherosclerosis (rcdc), Heart Disease - Coronary Heart Disease, Leukocyte (mesh), 31 Biological Sciences (for-2020), Cardiovascular (hrcs-hc), Genetics (rcdc), Genotype (mesh), Human Genome, Cell Adhesion (mesh), 2.1 Biological and endogenous factors (hrcs-rac), Leukocyte, Atherosclerosis, Human Genome (rcdc), cardiovascular diseases, Atherosclerosis (mesh), Female (mesh), genome-wide association studies, Energy Metabolism, Developmental Biology, CARDIoGRAMplusC4D, Genome-Wide Association Study
Male, Aging, 3102 Bioinformatics and computational biology (for-2020), Vascular (mesh), 3001 Agricultural biotechnology (for-2020), Energy Metabolism (mesh), Coronary Artery Disease, Cardiovascular, 11 Medical and Health Sciences (for), Medical and Health Sciences, 3105 Genetics (for-2020), Muscle, Smooth, Vascular, Aging (rcdc), Clinical Research (rcdc), Risk Factors, 2.1 Biological and endogenous factors, Male (mesh), Genetic Predisposition to Disease (mesh), Histone Code (mesh), EPIC-CVD, Developmental Biology (science-metrix), Coronary Artery Disease (mesh), Humans (mesh), Chemotaxis, Single Nucleotide, Arteries, Biological Sciences, Bioinformatics and computational biology, 06 Biological Sciences (for), Histone Code, Chemotaxis, Leukocyte, Heart Disease, Muscle, Cardiovascular (rcdc), Genome-Wide Association Study (mesh), Female, Smooth, Quantitative Trait Loci (mesh), Single Nucleotide (mesh), Genotype, Agricultural biotechnology, Quantitative Trait Loci, Heart Disease (rcdc), 610, Heart Disease - Coronary Heart Disease (rcdc), Polymorphism, Single Nucleotide, Arteries (mesh), Clinical Research, Risk Factors (mesh), Vascular, Genetics, Journal Article, Cell Adhesion, Humans, Genetic Predisposition to Disease, Polymorphism, Atherosclerosis (rcdc), Heart Disease - Coronary Heart Disease, Leukocyte (mesh), 31 Biological Sciences (for-2020), Cardiovascular (hrcs-hc), Genetics (rcdc), Genotype (mesh), Human Genome, Cell Adhesion (mesh), 2.1 Biological and endogenous factors (hrcs-rac), Leukocyte, Atherosclerosis, Human Genome (rcdc), cardiovascular diseases, Atherosclerosis (mesh), Female (mesh), genome-wide association studies, Energy Metabolism, Developmental Biology, CARDIoGRAMplusC4D, Genome-Wide Association Study
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