Abstract
Objective: Despite alarming obesity levels in the Arabian Peninsula, its population lacks convincingly identified genetic determinants of obesity. A genome-wide association study was performed for obesity-related anthropometric traits in Arabs and to decipher mechanisms by which the variants mediate traits. Methods: The Illumina HumanOmniExpress BeadChip was used to genotype 1,353 Arab individuals (largely with Class I obesity) from Kuwait. Genome-wide association tests for obesity-related anthropometric traits were performed. Top associations were tested for replication in an independent cohort (1,176 unrelated Arabs). Resultant variants were investigated for interactions with obesity-related plasma biomarkers. Pathway analysis was performed on genes harboring markers in linkage disequilibrium (LD) with identified variants. Results: The rs9606756[c.67A>G,p.Ile23Val] variant from TCN2 was associated with waist circumference (WC) at nearly genome-wide significance (P = 8.92E−08). WC was inversely related with Apo-A1 or high-density lipoprotein levels; individuals with the AG genotype exhibited stronger relationship than those with the reference AA genotype. Interaction involving the AG genotype (effect allele = G) significantly contributed to an increase in anthropometric traits (particularly WC). Genes harboring single-nucleotide polymorphisms in LD with rs9606756 mapped onto an interaction network (with TP53 as central element) of established obesity/diabetes-related protein components. Conclusions: The TCN2 variant acts as a risk factor for WC in the Arab population. The variant mediates obesity-related anthropometric traits via interactions with Apo-A1/high-density lipoprotein or TP53.
Original language | English |
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Pages (from-to) | 1098-1108 |
Number of pages | 11 |
Journal | Obesity |
Volume | 25 |
Issue number | 6 |
DOIs | |
Publication status | Published - 1 Jun 2017 |