Sex-specific genetic effects across biomarkers

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Author(s)

Author Name

Emily Flynn

Published 3 Projects

Bioinformatics Genetics

Yosuke Tanigawa

Published 2 Projects

Genetics

Fatima Rodriguez

Published 1 Project

Genetics

Nasa Sinnott-Armstrong

Published 1 Project

Genetics

Manuel A Rivas

Published 3 Projects

Genetics

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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, 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 444 male-specific variants. These include protein-altering variants in steroid hormone production genes (POR, CYP3A43, 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 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.

Genetics
Genetics 59 Projects