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Genetics and Epigenetics

Multiple genetic variations confer risks for obesity and type 2 diabetes mellitus in arab descendants from UAE

International Journal of Obesity volume 42, pages 1345–1353 (2018)Cite this article

Subjects

Abstract

Background

The United Arab Emirates (UAE) is one of the countries most threatened with obesity. Here we investigated associations between hundreds of single-nucleotide polymorphisms (SNPs) and the following obesity indicators: body mass index (BMI), waist circumference (WC), and height. We also investigated the associations between obesity-related genes with type 2 diabetes mellitus (T2DM).

Methods

We tested 87, 58, and 586 SNPs in a previous genome-wide significance level for associations with BMI (n = 880), WC (n = 455), and height (n = 897), respectively. For each trait, we used normally transformed Z scores and tested them with SNPs using linear regression models that incorporated age and gender as covariates. The weighted polygenic risk scores for significant SNPs for each trait were tested with the corresponding Z scores using linear regression models with the same covariates. We further tested 145 obesity loci with T2DM (464 cases, 415 controls) using a logistic regression model including age, gender, and BMI Z scores as covariates.

Results

The Mean BMI was 29.39 kg/m2, and mean WC was 103.66 cm. Hypertension and dyslipidemia were common obesity comorbidities (>60%). The best associations for BMI was in FTO, LOC284260 and USP37, and for WC in RFX7 and MYEOV. For height, the best association was in NSD1 followed by MFAP2 and seven other loci. The polygenic scores revealed stronger associations for each trait than individual SNPs; although they could only explain <1% of the traits’ Z scores variations. For T2DM, the strongest associations were with the TCF7L2 and MC4R loci (P < 0.01, OR ~1.70), with novel associations detected with KCNK3 and RARB.

Conclusions

In this first study of Arab descendants, we confirmed several known obesity (FTO, USP37, and RFX7), height (NSD1, MFAP2), and T2DM (TCF7L2, MC4R) associations; and report novel associations, like KCNK3 and RARB for T2DM.

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Acknowledgements

We gratefully acknowledge the contribution of participating individuals whose cooperation made this study possible.

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Authors and Affiliations

  1. Khalifa University Center of Biotechnology, Abu Dhabi, United Arab Emirates

    Wael Osman, Guan K Tay & Habiba Alsafar

  2. School of Health and Medical Sciences, Edith Cowan University, Joondalup, WA, Australia

    Guan K Tay

  3. School of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley, WA, Australia

    Guan K Tay

  4. Department of Biomedical Engineering, Khalifa University, Abu Dhabi, United Arab Emirates

    Habiba Alsafar

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  1. Wael Osman
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Correspondence to Habiba Alsafar.

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Osman, W., Tay, G.K. & Alsafar, H. Multiple genetic variations confer risks for obesity and type 2 diabetes mellitus in arab descendants from UAE. Int J Obes 42, 1345–1353 (2018). https://doi.org/10.1038/s41366-018-0057-6

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