Differential association of 53 genome-wide association studies identified loci with type 2 diabetes in Lebanese and Tunisian Arabs

Kuralay Atageldiyeva, Wassim Almawi

Research output: Chapter in Book/Report/Conference proceedingConference contribution

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Background and Aims: Type 2 diabetes (T2DM) is a leading health problem in developing and developed countries, and is caused by modifiable and non-modifiable factors, including genetic predisposition, and interaction between both factors. Previous investigation of T2DM susceptibility genes utilized the “candidate gene” approach, which was superseded by the genome-wide association studies (GWAS) approach. Several T2DM susceptibility loci were identified in European populations, and later confirmed in other ethnic groups. These totaled 88 for T2DM, and further 83 for glycemic traits. We aimed to iIdentify candidate genes associated with Type 2 diabetes in distinct Arab-speaking populations, which can be used as marker of diabetes and its complications.
Materials and methods. We analyzed GWAS identified SNPs in a Tunisian (North Africa) and Lebanese (Eastern Mediterranean) Arab representatives (751 diagnosed with T2D and 918 matched controls among Lebanese vs 1470 diabetic and 838 controls among Tunisian) for association with T2D and diabetes related quantitative traits. We tested association between candidate SNPs and status of T2D using logistic regression with age, sex and BMI as covariates. The study-wide significance was determined by applying Bonferroni correction using 28 tested SNPs (P value of 1.8x10-3 ).
Results. This provided new insights into the genetic aspects of T2DM, and inter-individual variation in glycemic traits, such as glucose, insulin, pro-insulin and HbA1c levels. In view of the heterogeneity of Arab-speaking populations, which comprises people of distinct ethnicities, and whose origins can be classified according to their area of habitation, replication studies on Tunisian (North Africa) and Lebanese (Eastern Mediterranean) Arabs confirmed the association of common GWAS at-risk loci with altered T2DM risk in both communities, which included TCF7L2. However, differential association with T2DM of other loci, including IGF2BP2, KCNJ11, PPARγ and SLC30A8, was also noted between Lebanese and Tunisian Arabs.
Conclusion. Our findings confirm substantial overlap of T2DM at-risk loci across many ethnic groups, and also to unique association of T2DM variants disease prevalence in select communities. More studies using meta-analysis, along with gene-environment, functional, epigenetic, and next generation sequencing (NGS) analysis, are needed to establish the relevance of this differential association on T2DM in these communities.
Original languageEnglish
Title of host publication57th European Association for the Study of Diabetes Annual meeting
PublisherSpringer Nature
Number of pages1
ISBN (Electronic)1432-0428
ISBN (Print)0012-186X
Publication statusPublished - Sep 1 2019


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