Combined analysis of studies with East Asian participants yields a dramatic increase in knowledge of type 2 diabetes genetics
Bringing together information from multiple genetic studies of type 2 diabetes in people of East Asian descent has yielded a wealth of new information about the disease that may one day help improve its treatment and prevention for people whether or not they have East Asian genetic heritage. Understanding genetic risk for type 2 diabetes has grown in importance in recent decades as lifestyle changes have interacted with genetic traits that might have been benign in prior generations, but now predispose a person to type 2 diabetes. This dynamic is helping fuel a worrisome rise in diabetes prevalence around the world, and East Asian countries are seeing some of the largest increases. Researchers have identified over 240 different genetic regions—mostly within the last 15 years—where variations appear to have a measurable influence on susceptibility to type 2 diabetes. Most of these advances came from genome-wide association (GWA) studies, in which scientists look for genetic features that are either more or less common in people with a disease than in people without it. By themselves, most of the known diabetes risk genes have only small effects on a person’s likelihood of getting the disease, and early GWA studies often required genomic analysis of thousands of participants in order to detect them. As the field progressed, even larger studies were required to find genes with still smaller effects, or for which the variants of interest were rarer. Eventually, the only practical way to obtain a large enough sample size was to combine results from several previous studies so that hundreds of thousands of research participants were effectively included. The great majority of type 2 diabetes susceptibility genes found in this manner, however, were identified by combining GWA studies whose participants were primarily of European ancestry. As a result, less is known about unique genetic risk factors for the disease in people of East Asian and other non-White backgrounds.
Researchers have now completed a pooled analysis of numerous previous GWA studies conducted in Japan, China, Korea, and other East Asian countries, yielding a cumulative total of 433,540 participants, 77,418 of whom had type 2 diabetes. In this way they identified 183 different parts of the genome where genetic features influence predisposition to type 2 diabetes in people with ancestry from this part of the world. Most of these genetic regions had been identified in previous studies as affecting the risk for type 2 diabetes, confirming and bolstering what was known about the relationship of those gene regions to the disease. However, a remarkably large number—61—could be clearly distinguished from previously detected type 2 diabetes genetic risk factors, and were therefore new discoveries. Some of the gene regions newly linked to type 2 diabetes risk were notable for affecting susceptibility to the disease even in participants considered to have a healthy body weight. These findings may help explain an intriguing scientific mystery: although overweight and obesity are risk factors for type 2 diabetes throughout the world, people with East Asian ancestry are more likely than those from other backgrounds to develop type 2 diabetes at lower body weight. Increasing the number of known genetic risk factors for type 2 diabetes by about 25 percent, this study sheds light on aspects of type 2 diabetes genetics that are unique to those of East Asian descent and may someday make it possible to tailor diabetes prevention or care for a large fraction of the world’s population. The findings have also reinforced and clarified previous discoveries in participants from other parts of the world and yielded information that could eventually lead to new therapeutic approaches with potential to benefit anyone with type 2 diabetes, regardless of where his or her ancestors come from.
Spracklen CN, Horikoshi M, Kim YJ,…Sim X. Identification of type 2 diabetes loci in 433,540 East Asian individuals. Nature 582: 240- 245, 2020.