Identification of genetic effects underlying type 2 diabetes in South Asian and European populations
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Published:2022-04-07
Issue:1
Volume:5
Page:
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ISSN:2399-3642
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Container-title:Communications Biology
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language:en
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Short-container-title:Commun Biol
Author:
Loh MarieORCID, Zhang WeihuaORCID, Ng Hong Kiat, Schmid KatharinaORCID, Lamri AmelORCID, Tong Lin, Ahmad Meraj, Lee Jung-Jin, Ng Maggie C. Y.ORCID, Petty Lauren E., Spracklen Cassandra N.ORCID, Takeuchi FumihikoORCID, Islam Md. Tariqul, Jasmine Farzana, Kasturiratne Anuradhani, Kibriya MuhammadORCID, Mohlke Karen L.ORCID, Paré GuillaumeORCID, Prasad Gauri, Shahriar Mohammad, Chee Miao Ling, de Silva H. Janaka, Engert James C.ORCID, Gerstein Hertzel C., Mani K. Radha, Sabanayagam CharumathiORCID, Vujkovic MarijanaORCID, Wickremasinghe Ananda R.ORCID, Wong Tien Yin, Yajnik Chittaranjan S., Yusuf Salim, Ahsan Habibul, Bharadwaj Dwaipayan, Anand Sonia S.ORCID, Below Jennifer E.ORCID, Boehnke MichaelORCID, Bowden Donald W., Chandak Giriraj R., Cheng Ching-YuORCID, Kato Norihiro, Mahajan Anubha, Sim XuelingORCID, McCarthy Mark I., Morris Andrew P., Kooner Jaspal S.ORCID, Saleheen DanishORCID, Chambers John C.ORCID
Abstract
AbstractSouth Asians are at high risk of developing type 2 diabetes (T2D). We carried out a genome-wide association meta-analysis with South Asian T2D cases (n = 16,677) and controls (n = 33,856), followed by combined analyses with Europeans (neff = 231,420). We identify 21 novel genetic loci for significant association with T2D (P = 4.7 × 10−8 to 5.2 × 10−12), to the best of our knowledge at the point of analysis. The loci are enriched for regulatory features, including DNA methylation and gene expression in relevant tissues, and highlight CHMP4B, PDHB, LRIG1 and other genes linked to adiposity and glucose metabolism. A polygenic risk score based on South Asian-derived summary statistics shows ~4-fold higher risk for T2D between the top and bottom quartile. Our results provide further insights into the genetic mechanisms underlying T2D, and highlight the opportunities for discovery from joint analysis of data from across ancestral populations.
Publisher
Springer Science and Business Media LLC
Subject
General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)
Reference100 articles.
1. International Diabetes Federation. IDF Diabetes Atlas 8th edn. (International Diabetes Federation, 2017). 2. United Nations. World Population Prospects: The 2019 Revision (United Nations, 2019). 3. Kooner, J. S. et al. Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci. Nat. Genet. 43, 984–989 (2011). 4. Sattar, N. & Gill, J. M. Type 2 diabetes in migrant south Asians: mechanisms, mitigation, and management. Lancet Diabetes Endocrinol. 3, 1004–1016 (2015). 5. Zheng, Y., Ley, S. H. & Hu, F. B. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat. Rev. Endocrinol. 14, 88–98 (2018).
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