Contribution of genetics to visceral adiposity and its relation to cardiovascular and metabolic disease

Nat Med. 2019 Sep;25(9):1390-1395. doi: 10.1038/s41591-019-0563-7. Epub 2019 Sep 9.


Visceral adipose tissue (VAT)-fat stored around the internal organs-has been suggested as an independent risk factor for cardiovascular and metabolic disease1-3, as well as all-cause, cardiovascular-specific and cancer-specific mortality4,5. Yet, the contribution of genetics to VAT, as well as its disease-related effects, are largely unexplored due to the requirement for advanced imaging technologies to accurately measure VAT. Here, we develop sex-stratified, nonlinear prediction models (coefficient of determination = 0.76; typical 95% confidence interval (CI) = 0.74-0.78) for VAT mass using the UK Biobank cohort. We performed a genome-wide association study for predicted VAT mass and identified 102 novel visceral adiposity loci. Predicted VAT mass was associated with increased risk of hypertension, heart attack/angina, type 2 diabetes and hyperlipidemia, and Mendelian randomization analysis showed visceral fat to be a causal risk factor for all four diseases. In particular, a large difference in causal effect between the sexes was found for type 2 diabetes, with an odds ratio of 7.34 (95% CI = 4.48-12.0) in females and an odds ratio of 2.50 (95% CI = 1.98-3.14) in males. Our findings bolster the role of visceral adiposity as a potentially independent risk factor, in particular for type 2 diabetes in Caucasian females. Independent validation in other cohorts is necessary to determine whether the findings can translate to other ethnicities, or outside the UK.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiposity / genetics*
  • Adult
  • Aged
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / genetics*
  • Cardiovascular Diseases / pathology
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / pathology
  • Female
  • Genome-Wide Association Study
  • Humans
  • Hypertension / genetics
  • Hypertension / metabolism
  • Hypertension / pathology
  • Intra-Abdominal Fat / metabolism*
  • Intra-Abdominal Fat / pathology
  • Male
  • Mendelian Randomization Analysis
  • Metabolic Diseases / epidemiology
  • Metabolic Diseases / genetics*
  • Metabolic Diseases / pathology
  • Middle Aged
  • Obesity / genetics
  • Obesity / metabolism
  • Obesity / pathology
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • Sex Characteristics