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

PLoS Genet. 2022 Jan 20;18(1):e1009952. doi: 10.1371/journal.pgen.1009952. eCollection 2022 Jan.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiposity / genetics*
  • Adult
  • Biological Specimen Banks
  • Cohort Studies
  • Female
  • GTPase-Activating Proteins / genetics
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study*
  • Humans
  • Male
  • Middle Aged
  • Nerve Tissue Proteins / genetics
  • Obesity / genetics
  • Overweight / genetics
  • Polymorphism, Single Nucleotide
  • Taiwan

Substances

  • GTPase-Activating Proteins
  • Nerve Tissue Proteins
  • RALGAPA1 protein, human

Grants and funding

WCC was supported by Ministry of Science and Technology, Taiwan (MOST110-2628-B-038-020 and MOST109-2628-B-038-012) and Taipei Medical University, Taiwan (12310-106079; Yusuke Nakamura Chair Professorship). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.