High genetic burden of type 2 diabetes can promote the high prevalence of disease: a longitudinal cohort study in Iran

Maryam Moazzam-Jazi,Asiyeh Sadat Zahedi,Maryam S Daneshpour,Leila Najd Hassan Bonab

doi:10.1038/s41598-020-70725-4

Abstract

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.

Highlights

Type 2 diabetes (T2D) is emerging as one of the serious public health issues in both developed and developing counties
To this end, (1) we collected a comprehensive list of T2D-associated SNPs and examined their allele frequencies differences between the Iranian population and each of 1,000 Genome Project populations, African (AFR), American (AMR), East Asian (EAS), European (EUR), and South Asian (SAS); (2) we identified the enriched or depleted risk alleles of T2D-associated SNPs in the Iranian and each of the 1,000 Genome Project populations compared to the global population; (3) we calculated the polygenic risk score (PRS) for the enriched risk alleles within the Iranian population and tested the PRS correlation with T2D prevalence and incidence in this population
The collected SNPs resulted from 21 GWA studies, which two studies conducted in African populations, three in East Asian populations, 12 in European, two in South Asians, and three in American populations

Summary

Introduction

Type 2 diabetes (T2D) is emerging as one of the serious public health issues in both developed and developing counties. 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. A large number of common and low-frequency T2D susceptibility variants have been characterized by the genome-wide association studies (GWAS) and the whole-genome sequencing[5,6,7,8,9]. Most of these variants are located near genes that were previously known to be involved in diabetes pathogenesis, such as TCF7L2, CDKAL1, CDKN1C, and IGF2BP210. The critical importance of the issue in society public health and the early-mentioned statistics regarding the T2D status in Iran motivated us to estimate the genetic burden of this disease in the Iranian population for the first time

Methods

Results

Conclusion