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.

"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 one of the authors. "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 another author. "These findings expand the number of genetic variants associated with diabetes and highlight the importance of studying different ancestries."

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.

http://news.unchealthcare.org/news/2020/may/first-in-kind-study-reveals-genetic-markers-of-type-2-diabetes-in-east-asians

https://www.nature.com/articles/s41586-020-2263-3