TY - JOUR
T1 - Identification of new susceptibility loci for type 2 diabetes and shared etiological pathways with coronary heart disease
AU - Zhao, Wei
AU - Rasheed, Asif
AU - Tikkanen, Emmi
AU - Lee, Jung-Jin
AU - Butterworth, Adam S
AU - Howson, Joanna M M
AU - Assimes, Themistocles L
AU - Chowdhury, Rajiv
AU - Orho-Melander, Marju
AU - Damrauer, Scott
AU - Small, Aeron
AU - Asma, Senay
AU - Imamura, Minako
AU - Yamauch, Toshimasa
AU - Chambers, John C
AU - Chen, Peng
AU - Sapkota, Bishwa R
AU - Shah, Nabi
AU - Jabeen, Sehrish
AU - Surendran, Praveen
AU - Lu, Yingchang
AU - Zhang, Weihua
AU - Imran, Atif
AU - Abbas, Shahid
AU - Majeed, Faisal
AU - Trindade, Kevin
AU - Qamar, Nadeem
AU - Mallick, Nadeem Hayyat
AU - Yaqoob, Zia
AU - Saghir, Tahir
AU - Rizvi, Syed Nadeem Hasan
AU - Memon, Anis
AU - Rasheed, Syed Zahed
AU - Memon, Fazal-Ur-Rehman
AU - Mehmood, Khalid
AU - Ahmed, Naveeduddin
AU - Qureshi, Irshad Hussain
AU - Tanveer-Us-Salam, null
AU - Iqbal, Wasim
AU - Malik, Uzma
AU - Mehra, Narinder
AU - Kuo, Jane Z
AU - Sheu, Wayne H-H
AU - Guo, Xiuqing
AU - Nielsen, Sune F
AU - Nordestgaard, Børge G
AU - Tybjaerg-Hansen, Anne
AU - Benn, Marianne
AU - Frikke-Schmidt, Ruth
AU - Kamstrup, Pia R
AU - CHD Exome+ Consortium
PY - 2017/10
Y1 - 2017/10
N2 - 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.
AB - 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.
KW - Asia
KW - Asian Continental Ancestry Group
KW - Biomarkers
KW - Comorbidity
KW - Coronary Disease
KW - Diabetes Mellitus, Type 2
KW - Europe
KW - European Continental Ancestry Group
KW - Genetic Loci
KW - Genetic Predisposition to Disease
KW - Genome-Wide Association Study
KW - HLA-DRB5 Chains
KW - Humans
KW - Metabolic Networks and Pathways
KW - Metabolic Syndrome
KW - Molecular Targeted Therapy
KW - Mutation, Missense
KW - Polymorphism, Single Nucleotide
KW - Risk Factors
KW - Comparative Study
KW - Journal Article
U2 - 10.1038/ng.3943
DO - 10.1038/ng.3943
M3 - Journal article
C2 - 28869590
SN - 1061-4036
VL - 49
SP - 1450
EP - 1457
JO - Nature Genetics
JF - Nature Genetics
IS - 10
ER -