Genome-wide association study of body fat distribution identifies adiposity loci and sex-specific genetic effects

Nat Commun. 2019 Jan 21;10(1):339. doi: 10.1038/s41467-018-08000-4.

Abstract

Body mass and body fat composition are of clinical interest due to their links to cardiovascular- and metabolic diseases. Fat stored in the trunk has been suggested to be more pathogenic compared to fat stored in other compartments. In this study, we perform genome-wide association studies (GWAS) for the proportion of body fat distributed to the arms, legs and trunk estimated from segmental bio-electrical impedance analysis (sBIA) for 362,499 individuals from the UK Biobank. 98 independent associations with body fat distribution are identified, 29 that have not previously been associated with anthropometric traits. A high degree of sex-heterogeneity is observed and the effects of 37 associated variants are stronger in females compared to males. Our findings also implicate that body fat distribution in females involves mesenchyme derived tissues and cell types, female endocrine tissues as well as extracellular matrix maintenance and remodeling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / chemistry
  • Adipose Tissue / metabolism*
  • Anthropometry
  • Arm / anatomy & histology
  • Biological Specimen Banks
  • Body Fat Distribution*
  • Body Mass Index
  • Body Weight
  • Electric Impedance
  • Endocrine Glands / chemistry
  • Endocrine Glands / metabolism
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Genetic Heterogeneity
  • Genetic Loci*
  • Genome-Wide Association Study
  • Humans
  • Leg / anatomy & histology
  • Male
  • Obesity / genetics*
  • Obesity / metabolism
  • Obesity / pathology
  • Polymorphism, Single Nucleotide*
  • Sex Factors
  • Torso / anatomy & histology
  • United Kingdom
  • Waist-Hip Ratio