Genome-wide association study identifies genetic risk loci for adiposity in a Taiwanese population

Overweight and obese are risk factors for various diseases. In Taiwan, the combined prevalence of overweight and obesity has increased dramatically. Here, we conducted a genome-wide association study (GWAS) on four adiposity traits, including body-mass index (BMI), body fat percentage (BF%), waist circumference (WC), and waist-hip ratio (WHR), using the data for more than 21,000 subjects in Taiwan Biobank. Associations were evaluated between 6,546,460 single-nucleotide polymorphisms (SNPs) and adiposity traits, yielding 13 genome-wide significant (GWS) adiposity-associated trait-loci pairs. A known gene, FTO, as well as two BF%-associated loci (GNPDA2-GABRG1 [4p12] and RNU6-2-PIAS1 [15q23]) were identified as pleiotropic effects. Moreover, RALGAPA1 was found as a specific genetic predisposing factor to high BMI in a Taiwanese population. Compared to other populations, a slightly lower heritability of the four adiposity traits was found in our cohort. Surprisingly, we uncovered the importance of neural pathways that might influence BF%, WC and WHR in the Taiwanese (East Asian) population. Additionally, a moderate genetic correlation between the WHR and BMI (gamma(g) = 0.52; p = 2.37x10(-9)) was detected, suggesting different genetic determinants exist for abdominal adiposity and overall adiposity. In conclusion, the obesity-related genetic loci identified here provide new insights into the genetic underpinnings of adiposity in the Taiwanese population. Author summaryOverweight and obese individuals are at risk for various medical conditions in Taiwan. Thus, we performed a genome-wide association study (GWAS) on four adiposity traits, including body-mass index (BMI), body fat percentage (BF%), waist circumference (WC), and waist-hip ratio (WHR), using information for more than 21,000 subjects from the Taiwan Biobank. We identified in total 13 genome-wide significant (GWS) adiposity-associated loci, which including well known genetic loci that associated with BMI, such as FTO. Additionally, we found RALGAPA1 as plausible specific susceptibility loci for BMI in Taiwanese. Surprisingly, pathway analysis revealing neuronal implication to BF%, WC and WHR in this population.

Automated summary

Being overweight and obese are risk factors for various diseases, and their prevalence in Taiwan has increased dramatically. Through a genome-wide association study, we identified 13 significant genetic loci associated with adiposity traits in a Taiwanese population. We also discovered specific susceptibility loci and neural pathways that may influence adiposity in this population.