The genetics of testosterone contributes to "femaleness/maleness" of cardiometabolic traits and type 2 diabetes

Int J Obes (Lond). 2022 Jan;46(1):235-237. doi: 10.1038/s41366-021-00960-w. Epub 2021 Sep 3.

Abstract

The genetic architecture of testosterone is highly distinct between sexes. Moreover, obesity is associated with higher testosterone in females but lower testosterone in males. Here, we ask whether male-specific testosterone variants are associated with a male pattern of obesity and type 2 diabetes (T2D) in females, and vice versa. In the UK Biobank, we conducted sex-specific genome-wide association studies and computed polygenic scores for total (PGSTT) and bioavailable testosterone (PGSBT). We tested sex-congruent and sex-incongruent associations between sex-specific PGSTs and metabolic traits, as well as T2D diagnosis. Female-specific PGSBT was associated with an elevated cardiometabolic risk and probability of T2D, in both sexes. Male-specific PGSTT was associated with traits conferring a lower cardiometabolic risk and probability of T2D, in both sexes. We demonstrate the value in considering polygenic testosterone as sex-related continuous traits, in each sex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Diabetes Mellitus, Type 2 / classification
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Female
  • Genetic Predisposition to Disease / epidemiology
  • Genetic Predisposition to Disease / genetics
  • Genome-Wide Association Study / methods
  • Genome-Wide Association Study / statistics & numerical data
  • Humans
  • Male
  • Metabolic Syndrome / classification
  • Metabolic Syndrome / complications*
  • Metabolic Syndrome / epidemiology
  • Middle Aged
  • Sex Differentiation / genetics*
  • Testosterone / analysis
  • Testosterone / metabolism*

Substances

  • Testosterone