Abstract
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 (γg = 0.52; p = 2.37×10−9) 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.
Highlights
Obesity and overweight result from energy imbalances, which cause excessive fat accumulation in the body
Due to similar results obtained for adiposity phenotypes, we further identified genetic correlations among the body-mass index (BMI), BF%, waist circumference (WC), and waist-hip ratio (WHR)
By comparing the single-nucleotide polymorphisms (SNPs) identified here with cataloged genomewide association study (GWAS) reports, we evaluate the pleiotropic effects of genes on adiposity phenotypes
Summary
Obesity and overweight result from energy imbalances, which cause excessive fat accumulation in the body. In Taiwan, the prevalence of being overweight and obese (Body-mass index 27 kg/m2) has grown from 11.8% to 22.0% in the past 25 years (1993~2014) [4]. Bodymass index (BMI) is a common non-invasive indicator of general adiposity, while waist circumference (WC) and the waist-hip ratio (WHR) are measurements of abdominal or visceral fat. Another index, body fat percentage (BF%), reflects fat accumulation in adipose tissues. These measurements associate with various morbidities, such as cardiovascular diseases [5,6], diabetes [5,7,8], and specific types of cancers [9,10,11]
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