학술논문
Identification of genetic effects underlying type 2 diabetes in South Asian and European populations
Document Type
Original Paper
Author
Loh, Marie; Zhang, Weihua; Ng, Hong Kiat; Schmid, Katharina; Lamri, Amel; Tong, Lin; Ahmad, Meraj; Lee, Jung-Jin; Ng, Maggie C. Y.; Petty, Lauren E.; Spracklen, Cassandra N.; Takeuchi, Fumihiko; Islam, Md. Tariqul; Jasmine, Farzana; Kasturiratne, Anuradhani; Kibriya, Muhammad; Mohlke, Karen L.; Paré, Guillaume; Prasad, Gauri; Shahriar, Mohammad; Chee, Miao Ling; de Silva, H. Janaka; Engert, James C.; Gerstein, Hertzel C.; Mani, K. Radha; Sabanayagam, Charumathi; Vujkovic, Marijana; Wickremasinghe, Ananda R.; Wong, Tien Yin; Yajnik, Chittaranjan S.; Yusuf, Salim; Ahsan, Habibul; Bharadwaj, Dwaipayan; Anand, Sonia S.; Below, Jennifer E.; Boehnke, Michael; Bowden, Donald W.; Chandak, Giriraj R.; Cheng, Ching-Yu; Kato, Norihiro; Mahajan, Anubha; Sim, Xueling; McCarthy, Mark I.; Morris, Andrew P.; Kooner, Jaspal S.; Saleheen, Danish; Chambers, John C.
Source
Communications Biology. 5(1)
Subject
Language
English
ISSN
2399-3642
Abstract
South 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.
Marie Loh, Weihua Zhang et al. use a genome-wide association study meta-analysis to examine variants associated with Type 2 diabetes (T2D) in South Asian and European ancestry cohorts. Their results provide further insights into the genetic mechanisms underlying T2D across ancestral populations.
Marie Loh, Weihua Zhang et al. use a genome-wide association study meta-analysis to examine variants associated with Type 2 diabetes (T2D) in South Asian and European ancestry cohorts. Their results provide further insights into the genetic mechanisms underlying T2D across ancestral populations.