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Genome-wide association study and trans-ethnic meta-analysis identify novel susceptibility loci for type 2 diabetes mellitus.

Authors :
Elashi, Asma A
Toor, Salman M
Umlai, Umm-Kulthum Ismail
Al-Sarraj, Yasser A
Taheri, Shahrad
Suhre, Karsten
Abou-Samra, Abdul Badi
Albagha, Omar M E
Source :
BMC Medical Genomics; 4/29/2024, Vol. 17 Issue 1, p1-12, 12p
Publication Year :
2024

Abstract

Background: The genetic basis of type 2 diabetes (T2D) is under-investigated in the Middle East, despite the rapidly growing disease prevalence. We aimed to define the genetic determinants of T2D in Qatar. Methods: Using whole genome sequencing of 11,436 participants (2765 T2D cases and 8671 controls) from the population-based Qatar Biobank (QBB), we conducted a genome-wide association study (GWAS) of T2D with and without body mass index (BMI) adjustment. Results: We replicated 93 known T2D-associated loci in a BMI-unadjusted model, while 96 known loci were replicated in a BMI-adjusted model. The effect sizes and allele frequencies of replicated SNPs in the Qatari population generally concurred with those from European populations. We identified a locus specific to our cohort located between the APOBEC3H and CBX7 genes in the BMI-unadjusted model. Also, we performed a transethnic meta-analysis of our cohort with a previous GWAS on T2D in multi-ancestry individuals (180,834 T2D cases and 1,159,055 controls). One locus in DYNC2H1 gene reached genome-wide significance in the meta-analysis. Assessing polygenic risk scores derived from European- and multi-ancestries in the Qatari population showed higher predictive performance of the multi-ancestry panel compared to the European panel. Conclusion: Our study provides new insights into the genetic architecture of T2D in a Middle Eastern population and identifies genes that may be explored further for their involvement in T2D pathogenesis. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
17558794
Volume :
17
Issue :
1
Database :
Complementary Index
Journal :
BMC Medical Genomics
Publication Type :
Academic Journal
Accession number :
176997919
Full Text :
https://doi.org/10.1186/s12920-024-01855-1