National Institute of Health

Scientists perform genomic analysis to uncover genetic factors and traits linked to type 2 diabetes among East Asian individuals

The prevalence of type 2 diabetes (T2D) represents a major challenge to global health. As current strategies for T2D management are suboptimal, greater insight into the causal factors is needed. Now, Korean scientists have adopted genome-wide association studies to discover genetic factors associated with T2D among East Asians. To date, this is the largest analysis of T2D data from East Asians, which will facilitate the early detection and treatment of the disease in this population.

Scientists perform the largest-ever genome-wide analysis of East Asians to provide novel insights into the genetic causes of type 2 diabetes

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Diabetes has been a public health concern for several decades. The most common type of this complex disorder, type 2 diabetes (T2D), is characterized by insulin resistance and impaired pancreatic cell function. As with many chronic disorders, it is now understood that the disease is caused by a combination of genetic predisposition and environmental variables. 

To discover the genetic loci (specific locations on a chromosome) associated with T2D, several large-scale studies, such as genome-wide association studies (GWAS), have been conducted. These studies largely considered people of European heritage. However, among individuals of similar physical characteristics, T2D is more prevalent in East Asians than in Europeans. As a result, when previous research findings were applied, the accuracy of disease prediction dropped as genetic architecture varied among ancestry groups.

In a study published in Nature, a team of scientists from Korea's National Institute of Health, led by Dr. Bong-Jo Kim, collaborated with the National University of Singapore and Japan's Institute of Physical and Chemical Research (RIKEN) to conduct a GWAS analysis of 433,540 East Asians, including Koreans. Dr. Kim emphasizes the significance of their study, "In order to develop precision medicine of value to Koreans, genetic studies on Koreans are required. Our study is the largest genetic analysis of T2D among East Asians, and it was performed on a much larger scale than prior East Asian genomic studies. This study, therefore, is very important in discovering new genes that influence the risk of developing T2D." The study was supported by grants from Korea Centers for Disease Control and Prevention (4845–301, 4851–302, 4851–307) and intramural grants from the Korea National Institute of Health (2016-NI73001-00, 2019-NG-053-00).

The scientists analyzed genome data from 23 cohort studies that contained information on 77,418 individuals with T2D and 356,122 healthy individuals. Among the studied populations, the genome information of Korean individuals was assessed using the Korea Biobank Array, which is a genome microarray optimized for studying Korean genomes. By analyzing the genomes of Koreans and other East Asians, the scientists identified 301 distinct T2D genetic signals at 183 loci. Among them, 61 loci were novel contributors to T2D susceptibility. They discovered new associations near the genes GDAP1, PTF1A, SIX3, ALDH2, and genes involved in muscle and adipose differentiation. At another locus, scientists noted two overlapping T2D genetic signals that impact two genes, NKX6-3 and ANK1, in different tissues.

A strong correlation was observed when genetic factors for T2D found in East Asian populations were compared to those found in European populations, offering additional insight into the underlying causes. When the findings of this study were applied to Korean participants, it was ascertained that the top 1% of high-risk individuals were almost eight times more prone to developing T2D than the rest of the population!

Dr. Kim hopes that their study will serve as a basis for developing customized precision medicine for T2D. He surmises, "The findings of our study enable preemptive and efficient prevention of diabetes. Moreover, we will be able to effectively manage this chronic disease through tailored health management and lifestyle interventions. This study, therefore, represents a major step forward in lowering socio-economic pressures and improving the quality of life affected by major chronic diseases, including diabetes ."

There is still a lot of work to be done, but huge strides have already been made, and the pace is sure to continue!

Reference

Authors                          Bong-Jo Kim¹, Cassandra N. Spracklen^2,3, Momoko Horikoshi⁴, Young Jin Kim¹, Kuang Lin⁵

Title of original paper     Identification of type 2 diabetes loci in 433,540 East Asian individuals

Journal                           Nature

DOI                                10.1038/s41586-020-2263-3

Affiliations                      ¹ Division of Genome Science, Department of Precision Medicine, National Institute of Health, Republic of Korea

                                      ²Department of Genetics, University of North Carolina at Chapel Hill, USA

                                      ³Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, USA

                                      ⁴Laboratory for Endocrinology, Metabolism and Kidney Diseases, RIKEN Centre for Integrative Medical Sciences, Japan 

                                      ⁵Nuffield Department of Population Health, University of Oxford, Oxford, UK

Funding information

This work was supported by grants from Korea Centers for Disease Control and Prevention (4845–301, 4851–302, 4851–307) and intramural grants from the Korea National Institute of Health (2016-NI73001-00, 2019-NG-053-00) 

About National Institute of Health in Korea 

The Korea National Institute of Health (KNIH), one of the major operating components of the Ministry of Health and Welfare, leads the nation’s medical research. Over the past seven decades, the KNIH has made unwavering efforts to enhance the public’s health and innovate biomedical research. The KNIH seeks to eradicate diseases and make people healthier. The KNIH establishes a scientific basis and evidence underlying health policy as well as provides national research infrastructures. We also promote public health research. To this end, we make efforts to enrich a health research environment by granting funds to research projects and keeping our resources, data, and facilities more open and accessible to researchers.

Website: http://www.nih.go.kr/eng/

About Bong-Jo Kim

Dr. Kim is a head of Division of Genome Science, Department of Precision Medicine, National Institute of Health, Korea. His work focuses on population-based genomics and multi-omics analysis of common complex diseases and rare diseases. He leads the Korea Biobank Array project, which is an established array of genome information obtained from about 200,000 Korean individuals.