Identification of new susceptibility loci for type 2 diabetes and shared etiological pathways with coronary heart disease.
Identification of new susceptibility loci for type 2 diabetes and shared etiological pathways with coronary heart disease.
- 2017
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.
English
1061-4036
*Coronary Disease/ge [Genetics]
*Diabetes Mellitus, Type 2/ge [Genetics]
*Genome-Wide Association Study
Asia/ep [Epidemiology]
Asian Continental Ancestry Group/ge [Genetics]
Biomarkers
Comorbidity
Coronary Disease/ep [Epidemiology]
Coronary Disease/et [Etiology]
Diabetes Mellitus, Type 2/dt [Drug Therapy]
Diabetes Mellitus, Type 2/ep [Epidemiology]
Diabetes Mellitus, Type 2/et [Etiology]
Europe/ep [Epidemiology]
European Continental Ancestry Group/ge [Genetics]
Genetic Loci/ge [Genetics]
Genetic Predisposition to Disease
HLA-DRB5 Chains/ge [Genetics]
Humans
Metabolic Networks and Pathways/ge [Genetics]
Metabolic Syndrome X/ep [Epidemiology]
Metabolic Syndrome X/ge [Genetics]
Molecular Targeted Therapy
Mutation, Missense
Polymorphism, Single Nucleotide
Risk Factors
MedStar Health Research Institute
Journal Article
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.
English
1061-4036
*Coronary Disease/ge [Genetics]
*Diabetes Mellitus, Type 2/ge [Genetics]
*Genome-Wide Association Study
Asia/ep [Epidemiology]
Asian Continental Ancestry Group/ge [Genetics]
Biomarkers
Comorbidity
Coronary Disease/ep [Epidemiology]
Coronary Disease/et [Etiology]
Diabetes Mellitus, Type 2/dt [Drug Therapy]
Diabetes Mellitus, Type 2/ep [Epidemiology]
Diabetes Mellitus, Type 2/et [Etiology]
Europe/ep [Epidemiology]
European Continental Ancestry Group/ge [Genetics]
Genetic Loci/ge [Genetics]
Genetic Predisposition to Disease
HLA-DRB5 Chains/ge [Genetics]
Humans
Metabolic Networks and Pathways/ge [Genetics]
Metabolic Syndrome X/ep [Epidemiology]
Metabolic Syndrome X/ge [Genetics]
Molecular Targeted Therapy
Mutation, Missense
Polymorphism, Single Nucleotide
Risk Factors
MedStar Health Research Institute
Journal Article