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

• Published in: PLoS genetics 2022-01, Vol.18 (1), p.e1009952-e1009952
• Main Authors: Wong, Henry Sung-Ching, Tsai, Szu-Yi, Chu, Hou-Wei, Lin, Min-Rou, Lin, Gan-Hong, Tai, Yu-Ting, Shen, Chen-Yang, Chang, Wei-Chiao
• Format: Article
• Language: English
• Subjects: Adipose tissue; Adipose tissues; Adiposity - genetics; Adult; Biobanks; Biological Specimen Banks; Biology and Life Sciences; Body fat; Body measurements; Body weight; Chromosome 4; Cohort Studies; Consortia; Diabetes; Epigenetics; Female; Gene loci; Genetic aspects; Genetic Predisposition to Disease; Genome-wide association studies; Genome-Wide Association Study; Genomes; GTPase-Activating Proteins - genetics; Heritability; Humans; Male; Medicine and Health Sciences; Metabolism; Middle Aged; Nerve Tissue Proteins - genetics; Obesity; Obesity - genetics; Observations; Overweight; Overweight - genetics; People and Places; Polymorphism, Single Nucleotide; Population genetics; Quantitative trait loci; Risk factors; Single-nucleotide polymorphism; Taiwan
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1009952

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.