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


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.

SUBMITTER: Zhao W 

PROVIDER: S-EPMC5844224 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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

Zhao Wei W   Rasheed Asif A   Tikkanen Emmi E   Lee Jung-Jin JJ   Butterworth Adam S AS   Howson Joanna M M JMM   Assimes Themistocles L TL   Chowdhury Rajiv R   Orho-Melander Marju M   Damrauer Scott S   Small Aeron A   Asma Senay S   Imamura Minako M   Yamauch Toshimasa T   Chambers John C JC   Chen Peng P   Sapkota Bishwa R BR   Shah Nabi N   Jabeen Sehrish S   Surendran Praveen P   Lu Yingchang Y   Zhang Weihua W   Imran Atif A   Abbas Shahid S   Majeed Faisal F   Trindade Kevin K   Qamar Nadeem N   Mallick Nadeem Hayyat NH   Yaqoob Zia Z   Saghir Tahir T   Rizvi Syed Nadeem Hasan SNH   Memon Anis A   Rasheed Syed Zahed SZ   Memon Fazal-Ur-Rehman FU   Mehmood Khalid K   Ahmed Naveeduddin N   Qureshi Irshad Hussain IH   Tanveer-Us-Salam   Iqbal Wasim W   Malik Uzma U   Mehra Narinder N   Kuo Jane Z JZ   Sheu Wayne H-H WH   Guo Xiuqing X   Hsiung Chao A CA   Juang Jyh-Ming J JJ   Taylor Kent D KD   Hung Yi-Jen YJ   Lee Wen-Jane WJ   Quertermous Thomas T   Lee I-Te IT   Hsu Chih-Cheng CC   Bottinger Erwin P EP   Ralhan Sarju S   Teo Yik Ying YY   Wang Tzung-Dau TD   Alam Dewan S DS   Di Angelantonio Emanuele E   Epstein Steve S   Nielsen Sune F SF   Nordestgaard Børge G BG   Tybjaerg-Hansen Anne A   Young Robin R   Benn Marianne M   Frikke-Schmidt Ruth R   Kamstrup Pia R PR   Jukema J Wouter JW   Sattar Naveed N   Smit Roelof R   Chung Ren-Hua RH   Liang Kae-Woei KW   Anand Sonia S   Sanghera Dharambir K DK   Ripatti Samuli S   Loos Ruth J F RJF   Kooner Jaspal S JS   Tai E Shyong ES   Rotter Jerome I JI   Chen Yii-Der Ida YI   Frossard Philippe P   Maeda Shiro S   Kadowaki Takashi T   Reilly Muredach M   Pare Guillaume G   Melander Olle O   Salomaa Veikko V   Rader Daniel J DJ   Danesh John J   Voight Benjamin F BF   Saleheen Danish D  

Nature genetics 20170904 10


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. J  ...[more]

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