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

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.

Steve Epstein | Chih-Cheng Hsu | Peng Chen | Olle Melander | I-Te Lee | Themistocles L Assimes | Ren-Hua Chung | Yik Ying Teo | Danish Saleheen | Nabi Shah | Naveeduddin Ahmed | Tzung-Dau Wang | Khalid Mehmood | Yingchang Lu | Marju Orho-Melander | Børge G Nordestgaard | Sune F Nielsen | Samuli Ripatti | Senay Asma | Robin Young | Praveen Surendran | John Danesh | Adam S Butterworth | Veikko Salomaa | Wei Zhao | Xiuqing Guo | J Wouter Jukema | Emmi Tikkanen | Takashi Kadowaki | Wasim Iqbal | John C Chambers | Yi-Jen Hung | Guillaume Pare | Dharambir K Sanghera | Thomas Quertermous | Naveed Sattar | Scott Damrauer | J. Danesh | T. Assimes | V. Salomaa | Y. Teo | W. Sheu | I. Lee | E. Tai | M. Reilly | D. Rader | K. Mehmood | N. Sattar | S. Ripatti | B. Voight | O. Melander | M. Orho-Melander | K. Taylor | J. Rotter | R. Chowdhury | B. Nordestgaard | Xiuqing Guo | J. Jukema | S. F. Nielsen | D. Saleheen | J. Kooner | E. Bottinger | J. Howson | Wei Zhao | S. Damrauer | Weihua Zhang | J. Chambers | R. Loos | E. Tikkanen | Y. Hung | C. Hsiung | T. Quertermous | D. Sanghera | A. Butterworth | Sonia S Anand | G. Paré | Yingchang Lu | D. Alam | M. Benn | E. Di Angelantonio | R. Frikke-Schmidt | P. R. Kamstrup | A. Rasheed | P. Surendran | A. Tybjaerg-hansen | R. Young | Chih-Cheng Hsu | R. Chung | Peng Chen | T. Kadowaki | W. Iqbal | N. Shah | S. Maeda | N. Mehra | Wen-Jane Lee | K. Liang | P. Frossard | J. Kuo | Jung-Jin Lee | Tzung-Dau Wang | J. Juang | M. Imamura | Faisal Majeed | N. H. Mallick | Fazal-ur-rehman Memon | R. Smit | B. Sapkota | S. Jabeen | Daniel J Rader | Benjamin F Voight | Rajiv Chowdhury | Ruth Frikke-Schmidt | Jerome I Rotter | E Shyong Tai | Ruth J F Loos | Weihua Zhang | Jaspal S Kooner | Emanuele Di Angelantonio | Shiro Maeda | Wayne H-H Sheu | A. Imran | S. Abbas | K. Trindade | N. Qamar | Zia Yaqoob | T. Saghir | S. N. H. Rizvi | A. Memon | S. Z. Rasheed | Naveeduddin Ahmed | Joanna M M Howson | Chao A Hsiung | Yii-Der Ida Chen | Sonia Anand | Kent D Taylor | S. Ralhan | Erwin P Bottinger | Muredach Reilly | Wen-Jane Lee | Marianne Benn | Asif Rasheed | Anne Tybjaerg-Hansen | Jane Z Kuo | Sarju Ralhan | Kae-Woei Liang | Senay Asma | Jung-Jin Lee | Aeron Small | Minako Imamura | Toshimasa Yamauch | Bishwa R Sapkota | Sehrish Jabeen | 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 | Irshad Hussain Qureshi | Tanveer-Us-Salam | Uzma Malik | Narinder Mehra | Jyh-Ming J Juang | Dewan S Alam | Pia R Kamstrup | Roelof Smit | Philippe Frossard | I. Qureshi | U. Malik | Y. Chen | Aeron M. Small | T. Yamauch | Tanveer-us-Salam | S. Epstein | Weihua Zhang | Rajiv Chowdhury | Wei Zhao | R. Loos | K. Taylor | Wei Zhao | Nabi Shah | K. Taylor | P. Kamstrup | E. di Angelantonio

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