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

<h3>Background</h3><p dir="ltr">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.</p><h3>Methods</h3><p dir...

وصف كامل

محفوظ في:
التفاصيل البيبلوغرافية
المؤلف الرئيسي: Asma A Elashi (18464133) (author)
مؤلفون آخرون: Salman M Toor (9279953) (author), Umm-Kulthum Ismail Umlai (12040352) (author), Yasser A Al-Sarraj (18464136) (author), Shahrad Taheri (57360) (author), Karsten Suhre (67967) (author), Abdul Badi Abou-Samra (9417977) (author), Omar M E Albagha (18295414) (author)
منشور في: 2024
الموضوعات:
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الوصف
الملخص:<h3>Background</h3><p dir="ltr">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.</p><h3>Methods</h3><p dir="ltr">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.</p><h3>Results</h3><p dir="ltr">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.</p><h3>Conclusion</h3><p dir="ltr">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.</p><p dir="ltr"><br></p><p dir="ltr">Correction: Genome-wide association study and trans-ethnic meta-analysis identify novel susceptibility loci for type 2 diabetes mellitus: <a href="https://dx.doi.org/10.1186/s12920-024-01903-w" target="_blank">https://dx.doi.org/10.1186/s12920-024-01903-w</a>, published online 16 May 2024.</p><h2>Other Information</h2><p dir="ltr">Published in: BMC Medical Genomics<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1186/s12920-024-01855-1" target="_blank">https://dx.doi.org/10.1186/s12920-024-01855-1</a></p>