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Comparative Study
. 2017 Oct;49(10):1450-1457.
doi: 10.1038/ng.3943. Epub 2017 Sep 4.

Identification of New Susceptibility Loci for Type 2 Diabetes and Shared Etiological Pathways With Coronary Heart Disease

Wei Zhao  1   2 Asif Rasheed  3 Emmi Tikkanen  4   5 Jung-Jin Lee  2 Adam S Butterworth  6 Joanna M M Howson  6 Themistocles L Assimes  7 Rajiv Chowdhury  6 Marju Orho-Melander  8 Scott Damrauer  9 Aeron Small  10 Senay Asma  11 Minako Imamura  12   13   14 Toshimasa Yamauch  15 John C Chambers  16   17   18 Peng Chen  19 Bishwa R Sapkota  20 Nabi Shah  3   21 Sehrish Jabeen  3 Praveen Surendran  6 Yingchang Lu  22   23   24 Weihua Zhang  16   17 Atif Imran  3 Shahid Abbas  25 Faisal Majeed  3 Kevin Trindade  2 Nadeem Qamar  26 Nadeem Hayyat Mallick  27 Zia Yaqoob  26 Tahir Saghir  26 Syed Nadeem Hasan Rizvi  26 Anis Memon  26 Syed Zahed Rasheed  28 Fazal-Ur-Rehman Memon  29 Khalid Mehmood  30 Naveeduddin Ahmed  31 Irshad Hussain Qureshi  32 Tanveer-Us-Salam  33 Wasim Iqbal  33 Uzma Malik  32 Narinder Mehra  34 Jane Z Kuo  35   36 Wayne H-H Sheu  37   38 Xiuqing Guo  36 Chao A Hsiung  39 Jyh-Ming J Juang  40 Kent D Taylor  36 Yi-Jen Hung  41 Wen-Jane Lee  42 Thomas Quertermous  7 I-Te Lee  37   38 Chih-Cheng Hsu  39 Erwin P Bottinger  22 Sarju Ralhan  43 Yik Ying Teo  19   44   45   46   47 Tzung-Dau Wang  40 Dewan S Alam  48 Emanuele Di Angelantonio  6 Steve Epstein  49 Sune F Nielsen  50 Børge G Nordestgaard  51   52 Anne Tybjaerg-Hansen  51   53 Robin Young  6 CHD Exome+ ConsortiumMarianne Benn  54 Ruth Frikke-Schmidt  53 Pia R Kamstrup  51 EPIC-CVD ConsortiumEPIC-Interact ConsortiumMichigan BiobankJ Wouter Jukema  54   55 Naveed Sattar  56 Roelof Smit  57 Ren-Hua Chung  39 Kae-Woei Liang  58 Sonia Anand  59 Dharambir K Sanghera  20   60   61 Samuli Ripatti  4   5   62   63 Ruth J F Loos  22   23   24 Jaspal S Kooner  16   18 E Shyong Tai  64 Jerome I Rotter  36 Yii-Der Ida Chen  36 Philippe Frossard  3 Shiro Maeda  12   13   14 Takashi Kadowaki  15 Muredach Reilly  65 Guillaume Pare  66 Olle Melander  8   67 Veikko Salomaa  62 Daniel J Rader  2   10 John Danesh  6   68   69 Benjamin F Voight  10   70   71 Danish Saleheen  1   2   3
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Free PMC article
Comparative Study

Identification of New Susceptibility Loci for Type 2 Diabetes and Shared Etiological Pathways With Coronary Heart Disease

Wei Zhao et al. Nat Genet. .
Free PMC article

Abstract

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.

Figures

Figure 1
Figure 1
A circular Manhattan plot summarizing the association results for the T2D scan. Black: Previously established T2D loci, Red: Previously unreported T2D loci from trans-ethnic meta-analysis, Blue: Previously unreported T2D loci from EUR only meta-analysis.

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