Sex-specific genetic effects across biomarkers.

TitleSex-specific genetic effects across biomarkers.
Publication TypeJournal Article
Year of Publication2021
AuthorsFlynn, E, Tanigawa, Y, Rodriguez, F, Altman, RB, Sinnott-Armstrong, N, Rivas, MA
JournalEur J Hum Genet
Date Published2021 Jan

Sex differences have been shown in laboratory biomarkers; however, the extent to which this is due to genetics is unknown. In this study, we infer sex-specific genetic parameters (heritability and genetic correlation) across 33 quantitative biomarker traits in 181,064 females and 156,135 males from the UK Biobank study. We apply a Bayesian Mixture Model, Sex Effects Mixture Model (SEMM), to Genome-wide Association Study summary statistics in order to (1) estimate the contributions of sex to the genetic variance of these biomarkers and (2) identify variants whose statistical association with these traits is sex-specific. We find that the genetics of most biomarker traits are shared between males and females, with the notable exception of testosterone, where we identify 119 female and 445 male-specific variants. These include protein-altering variants in steroid hormone production genes (POR, UGT2B7). Using the sex-specific variants as genetic instruments for Mendelian randomization, we find evidence for causal links between testosterone levels and height, body mass index, waist and hip circumference, and type 2 diabetes. We also show that sex-specific polygenic risk score models for testosterone outperform a combined model. Overall, these results demonstrate that while sex has a limited role in the genetics of most biomarker traits, sex plays an important role in testosterone genetics.

Alternate JournalEur J Hum Genet
PubMed ID32873964
PubMed Central IDPMC7794464
Grant ListR01HG010140 / / U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) /
R01 LM005652 / LM / NLM NIH HHS / United States
T15 LM007033 / LM / NLM NIH HHS / United States
R01 HG010140 / HG / NHGRI NIH HHS / United States
K01 HL144607 / HL / NHLBI NIH HHS / United States
U01 HG009080 / HG / NHGRI NIH HHS / United States
F31LM013053 / / U.S. Department of Health & Human Services | NIH | U.S. National Library of Medicine (NLM) /
R01 GM102365 / GM / NIGMS NIH HHS / United States
1K01HL144607 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) /
F31 LM013053 / LM / NLM NIH HHS / United States