Identification of genetic effects underlying type 2 diabetes in South Asian and European populations

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 significan...

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Main Authors: Loh, Marie, Zhang, Weihua, Ng, Hong Kiat, Schmid, Katharina, Lamri, Amel, Tong, Lin, Meraj Ahmad, Lee, Jung-Jin, Ng, Maggie C. Y., Petty, Lauren E., Spracklen, Cassandra N., Takeuchi, Fumihiko, Md. Tariqul Islam, Jasmine, Farzana, Kasturiratne, Anuradhani, Muhammad Kibriya, Mohlke, Karen L., Paré, Guillaume, Prasad, Gauri, Mohammad Shahriar, 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., Salim Yusuf, Habibul Ahsan, 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.
Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
Format: Article
Language:English
Published: 2022
Subjects:
Online Access:https://hdl.handle.net/10356/160910
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Institution: Nanyang Technological University
Language: English
id sg-ntu-dr.10356-160910
record_format dspace
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Medicine
Diabetes
Genetic Variation
spellingShingle Science::Medicine
Diabetes
Genetic Variation
Loh, Marie
Zhang, Weihua
Ng, Hong Kiat
Schmid, Katharina
Lamri, Amel
Tong, Lin
Meraj Ahmad
Lee, Jung-Jin
Ng, Maggie C. Y.
Petty, Lauren E.
Spracklen, Cassandra N.
Takeuchi, Fumihiko
Md. Tariqul Islam
Jasmine, Farzana
Kasturiratne, Anuradhani
Muhammad Kibriya
Mohlke, Karen L.
Paré, Guillaume
Prasad, Gauri
Mohammad Shahriar
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.
Salim Yusuf
Habibul Ahsan
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.
Identification of genetic effects underlying type 2 diabetes in South Asian and European populations
description 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.
author2 Lee Kong Chian School of Medicine (LKCMedicine)
author_facet Lee Kong Chian School of Medicine (LKCMedicine)
Loh, Marie
Zhang, Weihua
Ng, Hong Kiat
Schmid, Katharina
Lamri, Amel
Tong, Lin
Meraj Ahmad
Lee, Jung-Jin
Ng, Maggie C. Y.
Petty, Lauren E.
Spracklen, Cassandra N.
Takeuchi, Fumihiko
Md. Tariqul Islam
Jasmine, Farzana
Kasturiratne, Anuradhani
Muhammad Kibriya
Mohlke, Karen L.
Paré, Guillaume
Prasad, Gauri
Mohammad Shahriar
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.
Salim Yusuf
Habibul Ahsan
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.
format Article
author Loh, Marie
Zhang, Weihua
Ng, Hong Kiat
Schmid, Katharina
Lamri, Amel
Tong, Lin
Meraj Ahmad
Lee, Jung-Jin
Ng, Maggie C. Y.
Petty, Lauren E.
Spracklen, Cassandra N.
Takeuchi, Fumihiko
Md. Tariqul Islam
Jasmine, Farzana
Kasturiratne, Anuradhani
Muhammad Kibriya
Mohlke, Karen L.
Paré, Guillaume
Prasad, Gauri
Mohammad Shahriar
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.
Salim Yusuf
Habibul Ahsan
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.
author_sort Loh, Marie
title Identification of genetic effects underlying type 2 diabetes in South Asian and European populations
title_short Identification of genetic effects underlying type 2 diabetes in South Asian and European populations
title_full Identification of genetic effects underlying type 2 diabetes in South Asian and European populations
title_fullStr Identification of genetic effects underlying type 2 diabetes in South Asian and European populations
title_full_unstemmed Identification of genetic effects underlying type 2 diabetes in South Asian and European populations
title_sort identification of genetic effects underlying type 2 diabetes in south asian and european populations
publishDate 2022
url https://hdl.handle.net/10356/160910
_version_ 1759857981322690560
spelling sg-ntu-dr.10356-1609102023-03-05T16:53:46Z Identification of genetic effects underlying type 2 diabetes in South Asian and European populations Loh, Marie Zhang, Weihua Ng, Hong Kiat Schmid, Katharina Lamri, Amel Tong, Lin Meraj Ahmad Lee, Jung-Jin Ng, Maggie C. Y. Petty, Lauren E. Spracklen, Cassandra N. Takeuchi, Fumihiko Md. Tariqul Islam Jasmine, Farzana Kasturiratne, Anuradhani Muhammad Kibriya Mohlke, Karen L. Paré, Guillaume Prasad, Gauri Mohammad Shahriar 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. Salim Yusuf Habibul Ahsan 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. Lee Kong Chian School of Medicine (LKCMedicine) Science::Medicine Diabetes Genetic Variation 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. Ministry of Health (MOH) National Medical Research Council (NMRC) Published version J.C.C. is supported by the Singapore Ministry of Health’s National Medical Research Council under its Singapore. The SINDI study is supported by the National Medical Research Council (NMRC), Singapore (grants 0796/2003, 1176/2008, 1149/2008, STaR/0003/2008, 1249/2010, CG/ SERI/2010, CIRG/1371/2013, and CIRG/1417/2015), and Biomedical Research Council (BMRC), Singapore (08/1/35/19/550 and 09/1/35/19/616). 2022-08-10T08:32:07Z 2022-08-10T08:32:07Z 2022 Journal Article Loh, M., Zhang, W., Ng, H. K., Schmid, K., Lamri, A., Tong, L., Meraj Ahmad, Lee, J., Ng, M. C. Y., Petty, L. E., Spracklen, C. N., Takeuchi, F., Md. Tariqul Islam, Jasmine, F., Kasturiratne, A., Muhammad Kibriya, Mohlke, K. L., Paré, G., Prasad, G., ...Chambers, J. C. (2022). Identification of genetic effects underlying type 2 diabetes in South Asian and European populations. Communications Biology, 5(1), 329-. https://dx.doi.org/10.1038/s42003-022-03248-5 2399-3642 https://hdl.handle.net/10356/160910 10.1038/s42003-022-03248-5 35393509 2-s2.0-85128087036 1 5 329 en NMRC/STaR/0028/2017 NMRC/0796/2003 NMRC/1176/2008 NMRC/1149/2008 NMRC/STaR/0003/2008 NMRC/1249/2010 NMRC/CG/SERI/2010 NMRC/CIRG/1371/2013 NMRC/CIRG/1417/2015 BMRC/08/1/35/19/550 BMRC/09/1/35/19/616 Communications Biology © 2022 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/. application/pdf