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

Zhao, W. et al. (2017) Identification of new susceptibility loci for type 2 diabetes and shared etiological pathways with coronary heart disease. Nature Genetics, 49(10), pp. 1450-1457. (doi: 10.1038/ng.3943) (PMID:28869590)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Young, Dr Robin and Sattar, Professor Naveed
• Authors: Zhao, W., Rasheed, A., Tikkanen, E., Lee, J.-J., Butterworth, A. S., Howson, J. M. M., Assimes, T. L., Chowdhury, R., Orho-Melander, M., Damrauer, S., Small, A., Asma, S., Imamura, M., Yamauch, T., Chambers, J. C., Chen, P., Sapkota, B. R., Shah, N., Jabeen, S., Surendran, P., Lu, Y., Zhang, W., Imran, A., Abbas, S., Majeed, F., Trindade, K., Qamar, N., Mallick, N. H., Yaqoob, Z., Saghir, T., Rizvi, S. N. H., Memon, A., Rasheed, S. Z., Memon, F.-U.-R., Mehmood, K., Ahmed, N., Qureshi, I. H., Tanveer, U.-S., Iqbal, W., Malik, U., Mehra, N., Kuo, J. Z., Sheu, W. H.-H., Guo, X., Hsiung, C. A., Juang, J.-M. J., Taylor, K. D., Hung, Y.-J., Lee, W.-J., Quertermous, T., Lee, I.-T., Hsu, C.-C., Bottinger, E. P., Ralhan, S., Teo, Y. Y., Wang, T.-D., Alam, D. S., Di Angelantonio, E., Epstein, S., Nielsen, S. F., Nordestgaard, B. G., Tybjaerg-Hansen, A., Young, R., Benn, M., Frikke-Schmidt, R., Kamstrup, P. R., Jukema, J. W., Sattar, N., Smit, R., Chung, R.-H., Liang, K.-W., Anand, S., Sanghera, D. K., Ripatti, S., Loos, R. J. F., Kooner, J. S., Tai, E. S., Rotter, J. I., Chen, Y.-D. I., Frossard, P., Maeda, S., Kadowaki, T., Reilly, M., Pare, G., Melander, O., Salomaa, V., Rader, D. J., Danesh, J., Voight, B. F., and Saleheen, D.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
• Journal Name: Nature Genetics
• Publisher: Nature Publishing Group
• ISSN: 1061-4036
• ISSN (Online): 1546-1718
• Published Online: 04 September 2017
• Copyright Holders: Copyright © 2017 Nature America, Inc., part of Springer Nature
• First Published: First published in Nature Genetics 49(10): 1450-1457
• Publisher Policy: Reproduced in accordance with the publisher copyright policy