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Identification of new susceptibility loci for type 2 diabetes and shared etiological pathways with coronary heart disease

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  • Wei Zhao
  • Asif Rasheed
  • Emmi Tikkanen
  • Jung-Jin Lee
  • Adam S Butterworth
  • Joanna M M Howson
  • Themistocles L Assimes
  • Rajiv Chowdhury
  • Marju Orho-Melander
  • Scott Damrauer
  • Aeron Small
  • Senay Asma
  • Minako Imamura
  • Toshimasa Yamauch
  • John C Chambers
  • Peng Chen
  • Bishwa R Sapkota
  • Nabi Shah
  • Sehrish Jabeen
  • Praveen Surendran
  • Yingchang Lu
  • Weihua Zhang
  • Atif Imran
  • Shahid Abbas
  • Faisal Majeed
  • Kevin Trindade
  • Nadeem Qamar
  • Nadeem Hayyat Mallick
  • Zia Yaqoob
  • Tahir Saghir
  • Syed Nadeem Hasan Rizvi
  • Anis Memon
  • Syed Zahed Rasheed
  • Fazal-Ur-Rehman Memon
  • Khalid Mehmood
  • Naveeduddin Ahmed
  • Irshad Hussain Qureshi
  • Tanveer-Us-Salam
  • Wasim Iqbal
  • Uzma Malik
  • Narinder Mehra
  • Jane Z Kuo
  • Wayne H-H Sheu
  • Xiuqing Guo
  • Sune F Nielsen
  • Børge G Nordestgaard
  • Anne Tybjaerg-Hansen
  • Marianne Benn
  • Ruth Frikke-Schmidt
  • Pia R Kamstrup
  • CHD Exome+ Consortium
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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.

TidsskriftNature Genetics
Udgave nummer10
Sider (fra-til)1450-1457
Antal sider8
StatusUdgivet - okt. 2017

ID: 52188462