Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Sci Rep. 2020 Aug 19;10(1):14006. doi: 10.1038/s41598-020-70725-4.
Type 2 diabetes (T2D) is emerging as one of the serious public health issues in both developed and developing counties. Here, we surveyed the worldwide population differentiation in T2D-associated variants and assessed the genetic burden of the disease in an ongoing Tehran Cardio-Metabolic Genetic Study (TCGS) cohort represented the Iranian population. We found multiple SNPs that were significantly depleted or enriched in at least one of the five populations of 1,000 Genome Project (African, American, East Asian, European, and South Asian) as well as the Iranian population. Interestingly, TCF7L2, a well-known associated gene with T2D, harbors the highest number of enriched risk alleles almost in all populations except for East Asian, where this gene embraces the largest number of significantly depleted risk alleles. The polygenic risk score (PRS) of the enriched risk alleles was calculated for 1,867 diabetic and 2,855 non-diabetic participants in the TCGS cohort, interestingly demonstrating that the risk of developing T2D was almost two times higher in top PRS quintile compared with the lowest quintile after adjusting for other known risk factors.
2 型糖尿病（T2D）在发达国家和发展中国家都是一个严重的公共卫生问题。在这里，我们调查了与 T2D 相关变异在全球人群中的差异，并在一个代表伊朗人群的正在进行的德黑兰心脏代谢遗传研究（TCGS）队列中评估了该疾病的遗传负担。我们发现了多个 SNP，这些 SNP 在至少一个千基因组计划（非洲、美洲、东亚、欧洲和南亚）的五个人群中明显缺失或富集，以及伊朗人群。有趣的是，TCF7L2 是一个与 T2D 密切相关的基因，它拥有最多的富集风险等位基因，除了东亚，这个基因拥有最多的显著缺失的风险等位基因。在 TCGS 队列中，我们对 1867 名糖尿病患者和 2855 名非糖尿病患者计算了富集风险等位基因的多基因风险评分（PRS），有趣的是，在调整了其他已知风险因素后，与最低 PRS 五分位数相比，最高 PRS 五分位数患 T2D 的风险几乎高出两倍。
