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First-in-kind study reveals genetic markers of type 2 diabetes in East Asians

Date:
May 6, 2020
Source:
University of North Carolina Health Care
Summary:
This research shows how different populations of people share most of the genetic susceptibilities to developing type 2 diabetes but do have some different genetic variations that can make them more or less susceptible to developing the condition.
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In the largest study of its kind in any non-European population, an international team of researchers identified 301 distinct genetic signals at 183 loci, or specific positions on a chromosome, associated with type 2 diabetes in people from East Asia. Sixty-one of the loci were newly implicated in the predisposition for type 2 diabetes. They had not been implicated in previous genome-wide association studies (GWAS) conducted in people of European descent.

This research, published in Nature, shows how different populations of people share most of the genetic susceptibilities to developing type 2 diabetes but do have some different genetic variations that can make them more or less susceptible to developing the condition. This genome-wide meta-analysis of 433,540 East Asians, including 77,418 with type 2 diabetes, is the result of two research consortia -- AGEN (Asian Genetic Epidemiology Network) and DIAMANTE (DIabetes Meta-ANalysis of Trans-Ethnic association studies).

Ultimately, the goal of such studies is to identify potential genetic targets to treat or even cure the chronic metabolic disorder that affects more than 400 million adults worldwide, according to the International Diabetes Federation.

The international team of more than 100 researchers was led by scientists at five institutions, all co-senior authors of the Nature paper:

  • Xueling Sim, PhD, Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore;
  • Karen Mohlke, PhD, Department of Genetics, University of North Carolina at Chapel Hill School of Medicine;
  • Bong-Jo Kim, MD, PhD, Center for Genome Science, National Institute of Health, Cheongjusi, South Korea;
  • Robin Walters, PhD, Nuffield Department of Population Health, University of Oxford, United Kingdom;
  • Takashi Kadowaki, MD, PhD, Department of Diabetes and Metabolic Diseases, University of Tokyo, Japan.

"Such a large-scale study would never have been possible without the commitment and dedication to collaboration among so many scientists around the world, especially in Asia," said Karen Mohlke of UNC-Chapel Hill. "The data this team collected and analyzed has provided the research community with much-needed new information about the biological underpinnings of diabetes."

In the new analysis of East Asian individuals, researchers used genome-wide association data from 23 cohort studies in China, South Korea, Japan, Singapore, the Philippines, Hong Kong, Taiwan, and the United States to examine type 2 diabetes risk. For example, they found new associations near genes GDAP1, PTF1A, SIX3, ALDH2, and genes that affect muscle and adipose differentiation. At another locus, researchers found two overlapping type 2 diabetes genetic signals that appear to act through two genes, NKX6-3 and ANK1, in different tissues.

"We know diabetes is caused by a complex set of risk factors, such as BMI, that have varying effects on the disease across ancestries." said Xueling Sim, of the National University of Singapore. "These findings expand the number of genetic variants associated with diabetes and highlight the importance of studying different ancestries."

Co-first author Cassandra Spracklen, PhD, assistant professor of biostatistics and epidemiology at the University of Massachusetts at Amherst School of Public Health and Health Sciences, conducted many of the analyses for the Nature paper while a postdoctoral fellow in Mohlke's lab.

"Learning about the additional variants can help identify additional genes that influence a person's risk for developing type 2 diabetes" Spracklen said. "These genes teach us more about the pathophysiology of diabetes and could ultimately become therapeutic targets."

This research could help explain why -- among people of similar body mass index (BMI) or waist circumference -- the prevalence of type 2 diabetes is greater in East Asian populations than in European populations.

The next steps are to combine discovery across populations and to experimentally determine which genes are altered by the genetic variants and how those alterations lead to disease.


Story Source:

Materials provided by University of North Carolina Health Care. Note: Content may be edited for style and length.


Journal Reference:

  1. Cassandra N. Spracklen, Momoko Horikoshi, Young Jin Kim, Kuang Lin, Fiona Bragg, Sanghoon Moon, Ken Suzuki, Claudia H. T. Tam, Yasuharu Tabara, Soo-Heon Kwak, Fumihiko Takeuchi, Jirong Long, Victor J. Y. Lim, Jin-Fang Chai, Chien-Hsiun Chen, Masahiro Nakatochi, Jie Yao, Hyeok Sun Choi, Apoorva K. Iyengar, Hannah J. Perrin, Sarah M. Brotman, Martijn van de Bunt, Anna L. Gloyn, Jennifer E. Below, Michael Boehnke, Donald W. Bowden, John C. Chambers, Anubha Mahajan, Mark I. McCarthy, Maggie C. Y. Ng, Lauren E. Petty, Weihua Zhang, Andrew P. Morris, Linda S. Adair, Masato Akiyama, Zheng Bian, Juliana C. N. Chan, Li-Ching Chang, Miao-Li Chee, Yii-Der Ida Chen, Yuan-Tsong Chen, Zhengming Chen, Lee-Ming Chuang, Shufa Du, Penny Gordon-Larsen, Myron Gross, Xiuqing Guo, Yu Guo, Sohee Han, Annie-Green Howard, Wei Huang, Yi-Jen Hung, Mi Yeong Hwang, Chii-Min Hwu, Sahoko Ichihara, Masato Isono, Hye-Mi Jang, Guozhi Jiang, Jost B. Jonas, Yoichiro Kamatani, Tomohiro Katsuya, Takahisa Kawaguchi, Chiea-Chuen Khor, Katsuhiko Kohara, Myung-Shik Lee, Nanette R. Lee, Liming Li, Jianjun Liu, Andrea O. Luk, Jun Lv, Yukinori Okada, Mark A. Pereira, Charumathi Sabanayagam, Jinxiu Shi, Dong Mun Shin, Wing Yee So, Atsushi Takahashi, Brian Tomlinson, Fuu-Jen Tsai, Rob M. van Dam, Yong-Bing Xiang, Ken Yamamoto, Toshimasa Yamauchi, Kyungheon Yoon, Canqing Yu, Jian-Min Yuan, Liang Zhang, Wei Zheng, Michiya Igase, Yoon Shin Cho, Jerome I. Rotter, Ya-Xing Wang, Wayne H. H. Sheu, Mitsuhiro Yokota, Jer-Yuarn Wu, Ching-Yu Cheng, Tien-Yin Wong, Xiao-Ou Shu, Norihiro Kato, Kyong-Soo Park, E-Shyong Tai, Fumihiko Matsuda, Woon-Puay Koh, Ronald C. W. Ma, Shiro Maeda, Iona Y. Millwood, Juyoung Lee, Takashi Kadowaki, Robin G. Walters, Bong-Jo Kim, Karen L. Mohlke, Xueling Sim. Identification of type 2 diabetes loci in 433,540 East Asian individuals. Nature, 2020; DOI: 10.1038/s41586-020-2263-3

Cite This Page:

University of North Carolina Health Care. "First-in-kind study reveals genetic markers of type 2 diabetes in East Asians." ScienceDaily. ScienceDaily, 6 May 2020. <www.sciencedaily.com/releases/2020/05/200506133631.htm>.
University of North Carolina Health Care. (2020, May 6). First-in-kind study reveals genetic markers of type 2 diabetes in East Asians. ScienceDaily. Retrieved April 16, 2024 from www.sciencedaily.com/releases/2020/05/200506133631.htm
University of North Carolina Health Care. "First-in-kind study reveals genetic markers of type 2 diabetes in East Asians." ScienceDaily. www.sciencedaily.com/releases/2020/05/200506133631.htm (accessed April 16, 2024).

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