Repository logo
 

Using human genetics to understand the disease impacts of testosterone in men and women.

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Ruth, Katherine S 
Tyrrell, Jessica 
Thompson, Deborah J 
Wood, Andrew R 

Abstract

Testosterone supplementation is commonly used for its effects on sexual function, bone health and body composition, yet its effects on disease outcomes are unknown. To better understand this, we identified genetic determinants of testosterone levels and related sex hormone traits in 425,097 UK Biobank study participants. Using 2,571 genome-wide significant associations, we demonstrate that the genetic determinants of testosterone levels are substantially different between sexes and that genetically higher testosterone is harmful for metabolic diseases in women but beneficial in men. For example, a genetically determined 1 s.d. higher testosterone increases the risks of type 2 diabetes (odds ratio (OR) = 1.37 (95% confidence interval (95% CI): 1.22-1.53)) and polycystic ovary syndrome (OR = 1.51 (95% CI: 1.33-1.72)) in women, but reduces type 2 diabetes risk in men (OR = 0.86 (95% CI: 0.76-0.98)). We also show adverse effects of higher testosterone on breast and endometrial cancers in women and prostate cancer in men. Our findings provide insights into the disease impacts of testosterone and highlight the importance of sex-specific genetic analyses.

Description

Keywords

Biological Specimen Banks, Biomarkers, Body Composition, Breast Neoplasms, Cluster Analysis, Diabetes Mellitus, Type 2, Endometrial Neoplasms, Estradiol, Female, Genome-Wide Association Study, Genotype, Haplotypes, Humans, Male, Mendelian Randomization Analysis, Odds Ratio, Phenotype, Polycystic Ovary Syndrome, Polymorphism, Single Nucleotide, Prostatic Neoplasms, Sex Factors, Software, Testosterone, United Kingdom

Journal Title

Nat Med

Conference Name

Journal ISSN

1078-8956
1546-170X

Volume Title

26

Publisher

Springer Science and Business Media LLC

Rights

All rights reserved
Sponsorship
Medical Research Council (MC_UU_12015/2)
Medical Research Council (MC_UU_12015/1)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0617-10149)
MRC (MC_PC_13048)
Medical Research Council (MC_UU_00002/7)
MRC (MC_UU_00006/2)
Wellcome Trust (204623/Z/16/Z)
Medical Research Council (MC_PC_13048)
A.R.W. and T.M.F. are supported by the European Research Council grant: SZ-245 50371-GLUCOSEGENES-FP7-IDEAS-ERC. R.B. is funded by the Wellcome Trust and Royal Society grant 104150/Z/14/Z. J.T. is supported by the Academy of Medical Sciences Springboard award which is supported by the Wellcome Trust and GCRF [SBF004\1079]. This work was supported by the Medical Research Council [Unit Programme numbers MC_UU_12015/1 and MC_UU_12015/2].