Article open access publication

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

Nature Genetics, Springer Nature, ISSN 1061-4036

Volume 49, 10, 2017

DOI:10.1038/ng.3943, Dimensions: pub.1091430416, PMC: PMC5844224, PMID: 28869590,

Authors

Zhao, Wei (1)
Imamura, Minako (8) (9)
Chambers, John C (11) (12) (13)
Chen, Peng (14) (15)
Shah, Nabi (2) (17)
Lu, Yingchang (18) (19)
Zhang, Weihua (11) (12)
Kuo, Jane Z (30) (31)
Sheu, Wayne H-H (32) (33) (34)
Lee, I-Te (32) (33) (34)
Teo, Yik Ying (14) (15) (39) (40)
Jukema, J Wouter (47) (48)
Ripatti, Samuli (3) (51) (52)
Loos, Ruth J F (18) (19)
Kooner, Jaspal S (12) (13)
Maeda, Shiro (8) (9)
Danesh, John (4) (52)
Saleheen, Danish * (1) (2)

* Corresponding author

Affiliations

Organisations

  1. (1) University of Pennsylvania, grid.25879.31
  2. (2) Center for Non-Communicable Diseases, grid.497620.e
  3. (3) University of Helsinki, grid.7737.4
  4. (4) University of Cambridge, grid.5335.0
  5. (5) Stanford University, grid.168010.e
  6. (6) Lund University, grid.4514.4
  7. (7) McMaster University, grid.25073.33
  8. (8) Laboratory for Endocrinology, Metabolism, and Kidney Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
  9. (9) University of the Ryukyus, grid.267625.2
  10. (10) University of Tokyo, grid.26999.3d
  11. (11) Ealing Hospital NHS Trust, grid.412922.e
  12. (12) Imperial College London, grid.7445.2
  13. (13) Imperial College Healthcare NHS Trust, grid.417895.6
  14. (14) National University Health System, grid.410759.e
  15. (15) National University of Singapore, grid.4280.e
  16. (16) University of Oklahoma Health Sciences Center, grid.266902.9
  17. (17) COMSATS University Islamabad, grid.418920.6
  18. (18) Icahn School of Medicine at Mount Sinai, grid.59734.3c
  19. (19) Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
  20. (20) Faisalabad Institute of Cardiology, Faisalabad, Pakistan
  21. (21) National Institute of Cardiovascular Disorders, Karachi, Pakistan
  22. (22) Punjab Institute of Cardiology, grid.418815.1
  23. (23) Karachi Institute of Heart Diseases, grid.489028.f
  24. (24) Red Crescent Institute of Cardiology, Hyderabad, Pakistan
  25. (25) Civil Hospital Karachi, grid.414562.0
  26. (26) Liaquat National Hospital, grid.415915.d
  27. (27) King Edward Medical University, grid.412129.d
  28. (28) Lahore General Hospital, grid.415737.3
  29. (29) All India Institute of Medical Sciences, grid.413618.9
  30. (30) CardioDx (United States), grid.459412.f
  31. (31) Harbor–UCLA Medical Center, grid.239844.0
  32. (32) Taichung Veterans General Hospital, grid.410764.0
  33. (33) Chung Shan Medical University, grid.411641.7
  34. (34) National Yang Ming University, grid.260770.4
  35. (35) National Health Research Institutes, grid.59784.37
  36. (36) National Taiwan University Hospital, grid.412094.a
  37. (37) Division of Endocrinology and Metabolism, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
  38. (38) Hero DMC Heart Institute Ludhiana, Punjab, India
  39. (39) Genome Institute of Singapore, grid.418377.e
  40. (40) Singapore National Eye Center, grid.419272.b
  41. (41) International Centre for Diarrhoeal Disease Research, grid.414142.6
  42. (42) MedStar Washington Hospital Center, grid.415235.4
  43. (43) Frederiksberg Hospital, grid.415046.2, Capital Region
  44. (44) University of Copenhagen, grid.5254.6, KU
  45. (45) Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
  46. (46) Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  47. (47) Leiden University Medical Center, grid.10419.3d
  48. (48) Netherlands Heart Institute, grid.411737.7
  49. (49) University of Glasgow, grid.8756.c
  50. (50) Oklahoma Center for Neuroscience, Oklahoma City, Oklahoma, USA
  51. (51) National Institute for Health and Welfare, grid.14758.3f
  52. (52) Wellcome Sanger Institute, grid.10306.34
  53. (53) Columbia University, grid.21729.3f

Description

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.

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University of Copenhagen

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2017: Realized

Research area: Medicine

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2017: Level 2

Research area: Medicine

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Times Cited: 94

Field Citation Ratio (FCR): 19.9

Relative Citation ratio (RCR): 4.56

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Green, Accepted