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

• Published in: International Journal of Obesity 2018-07, Vol.42 (7), p.1345-1353
• Main Authors: Osman, Wael, Tay, Guan K, Alsafar, Habiba
• Format: Article
• Language: English
• Subjects: 45; 45/43; 45/61; 631/208/135; 692/163/2743/393; Body mass index; Body size; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Dyslipidemia; Epidemiology; Genetic diversity; Genomes; Health Promotion and Disease Prevention; Hypertension; Internal Medicine; Loci; Medicine; Medicine & Public Health; Metabolic Diseases; Obesity; Polygenic inheritance; Potassium channels; Public Health; Regression analysis; Regression models; Single-nucleotide polymorphism
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/s41366-018-0057-6

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/m 2 , 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