Identification of new susceptibility loci for type 2 diabetes and shared etiological pathways with coronary heart disease
Copyright policy )Identification of new susceptibility loci for type 2 diabetes and shared etiological pathways with coronary heart disease
To evaluate the shared genetic etiology of type 2 diabetes (T2D) and coronary heart disease (CHD), we conducted a genome-wide, multi-ancestry study of genetic variation for both diseases in up to 265,678 subjects for T2D and 260,365 subjects for CHD. We identify 16 previously unreported loci for T2D and 1 locus for CHD, including a new T2D association at a missense variant in HLA-DRB5 (odds ratio (OR) = 1.29). We show that genetically mediated increase in T2D risk also confers higher CHD risk. Joint T2D–CHD analysis identified eight variants—two of which are coding—where T2D and CHD associations appear to colocalize, including a new joint T2D–CHD association at the CCDC92 locus that also replicated for T2D. The variants associated with both outcomes implicate new pathways as well as targets of existing drugs, including icosapent ethyl and adipocyte fatty-acid-binding protein.
- University of Copenhagen Denmark
- McMaster University Canada
- Vanderbilt University United States
- National Institute of Health Pakistan
- Stanford University United States
Type 2 (mesh), EPIC-Interact Consortium, 3001 Agricultural biotechnology (for-2020), Europe (mesh), HLA-DRB5 Chains (mesh), ACID-BINDING PROTEIN, Comorbidity, VARIANTS, Cardiovascular, 11 Medical and Health Sciences (for), 3105 Genetics (for-2020), Missense (mesh), ARTERY-DISEASE, Molecular Targeted Therapy, European Continental Ancestry Group/genetics, Metabolic Syndrome (mesh), Comorbidity (mesh), Genetic Loci (mesh), Genetic Predisposition to Disease (mesh), 11 Medical and Health Sciences, Genetics & Heredity, Metabolic Networks and Pathways/genetics, Type 2/drug therapy, Metabolic Syndrome/epidemiology, Type 2, European Continental Ancestry Group, 610, Article, White People, Europe/epidemiology, GENETIC ARCHITECTURE, Asian People, Risk Factors (mesh), Genetics, Diabetes Mellitus, Humans, Comparative Study, Polymorphism, GENOME-WIDE ASSOCIATION, METAANALYSIS, AP2, 31 Biological Sciences (for-2020), Science & Technology, Asia/epidemiology, Genetics (rcdc), Prevention, 06 Biological Sciences, Human Genome (rcdc), Michigan Biobank, Metabolic and endocrine (hrcs-hc), Diabetes Mellitus, Type 2, Genetic Loci, Mutation, Biomarkers, Developmental Biology, Prevention (rcdc), 3102 Bioinformatics and computational biology (for-2020), 590, Coronary Disease, Medical and Health Sciences, Risk Factors, 2.1 Biological and endogenous factors, Asian People (mesh), White People (mesh), Coronary Disease/epidemiology, Developmental Biology (science-metrix), Asia (mesh), RISK, Metabolic Syndrome, Humans (mesh), CHD Exome+ Consortium, Metabolic Syndrome X, Diabetes, Single Nucleotide, Biological Sciences, HLA-DRB5 Chains/genetics, Bioinformatics and computational biology, 06 Biological Sciences (for), Europe, Biomarkers (mesh), Heart Disease, Genetic Loci/genetics, MENDELIAN RANDOMIZATION, Cardiovascular (rcdc), Genome-Wide Association Study (mesh), Coronary Disease (mesh), Metabolic Networks and Pathways (mesh), Life Sciences & Biomedicine, Metabolic Networks and Pathways, Asian Continental Ancestry Group, Molecular Targeted Therapy (mesh), Single Nucleotide (mesh), Asia, Agricultural biotechnology, Heart Disease (rcdc), Mutation, Missense, Heart Disease - Coronary Heart Disease (rcdc), Polymorphism, Single Nucleotide, EPIC-CVD Consortium, Journal Article, Asian Continental Ancestry Group/genetics, Genetic Predisposition to Disease, Obesity, Heart Disease - Coronary Heart Disease, Metabolic and endocrine, Obesity (rcdc), Cardiovascular (hrcs-hc), Human Genome, 2.1 Biological and endogenous factors (hrcs-rac), HLA-DRB5 Chains, ATHEROSCLEROSIS, Diabetes (rcdc), Missense, Genome-Wide Association Study
Type 2 (mesh), EPIC-Interact Consortium, 3001 Agricultural biotechnology (for-2020), Europe (mesh), HLA-DRB5 Chains (mesh), ACID-BINDING PROTEIN, Comorbidity, VARIANTS, Cardiovascular, 11 Medical and Health Sciences (for), 3105 Genetics (for-2020), Missense (mesh), ARTERY-DISEASE, Molecular Targeted Therapy, European Continental Ancestry Group/genetics, Metabolic Syndrome (mesh), Comorbidity (mesh), Genetic Loci (mesh), Genetic Predisposition to Disease (mesh), 11 Medical and Health Sciences, Genetics & Heredity, Metabolic Networks and Pathways/genetics, Type 2/drug therapy, Metabolic Syndrome/epidemiology, Type 2, European Continental Ancestry Group, 610, Article, White People, Europe/epidemiology, GENETIC ARCHITECTURE, Asian People, Risk Factors (mesh), Genetics, Diabetes Mellitus, Humans, Comparative Study, Polymorphism, GENOME-WIDE ASSOCIATION, METAANALYSIS, AP2, 31 Biological Sciences (for-2020), Science & Technology, Asia/epidemiology, Genetics (rcdc), Prevention, 06 Biological Sciences, Human Genome (rcdc), Michigan Biobank, Metabolic and endocrine (hrcs-hc), Diabetes Mellitus, Type 2, Genetic Loci, Mutation, Biomarkers, Developmental Biology, Prevention (rcdc), 3102 Bioinformatics and computational biology (for-2020), 590, Coronary Disease, Medical and Health Sciences, Risk Factors, 2.1 Biological and endogenous factors, Asian People (mesh), White People (mesh), Coronary Disease/epidemiology, Developmental Biology (science-metrix), Asia (mesh), RISK, Metabolic Syndrome, Humans (mesh), CHD Exome+ Consortium, Metabolic Syndrome X, Diabetes, Single Nucleotide, Biological Sciences, HLA-DRB5 Chains/genetics, Bioinformatics and computational biology, 06 Biological Sciences (for), Europe, Biomarkers (mesh), Heart Disease, Genetic Loci/genetics, MENDELIAN RANDOMIZATION, Cardiovascular (rcdc), Genome-Wide Association Study (mesh), Coronary Disease (mesh), Metabolic Networks and Pathways (mesh), Life Sciences & Biomedicine, Metabolic Networks and Pathways, Asian Continental Ancestry Group, Molecular Targeted Therapy (mesh), Single Nucleotide (mesh), Asia, Agricultural biotechnology, Heart Disease (rcdc), Mutation, Missense, Heart Disease - Coronary Heart Disease (rcdc), Polymorphism, Single Nucleotide, EPIC-CVD Consortium, Journal Article, Asian Continental Ancestry Group/genetics, Genetic Predisposition to Disease, Obesity, Heart Disease - Coronary Heart Disease, Metabolic and endocrine, Obesity (rcdc), Cardiovascular (hrcs-hc), Human Genome, 2.1 Biological and endogenous factors (hrcs-rac), HLA-DRB5 Chains, ATHEROSCLEROSIS, Diabetes (rcdc), Missense, Genome-Wide Association Study
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