Evaluating the genetic effects of sex hormone on the development of mental traits: a polygenic score analysis and genome-wide genetic interaction analysis in the UK Biobank cohort

Abstract

Objective: To evaluate the genetic effects of sex hormone on the development of mental traits.Methods: The SNPs significantly associated with sex hormone traits were driven from a two-stage genome-wide association study (GWAS). Four sex hormone were selected in this study, including sex hormone-binding globulin (SHBG), testosterone, bioavailable testosterone and estradiol. The polygenic risk scores (PRS) of sex hormone traits were calculated from individual-level genotype data of the UK Biobank cohort. We then used logistic and linear regression models to assess the associations between individual PRS of sex hormone traits and the frequency of alcohol consumption, anxiety, intelligence and so on. Finally, genome-wide genetic interaction study (GWGIS) was performed to detect novel candidate genes interacting with the sex hormone on the development of fluid intelligence and the frequency of smoking and alcohol consumption by PLINK2.0.Results: We observed positive associations between SHBG and the frequency of alcohol consumption (b=0.01, p=3.84×10–11) in males and females. In addition, estradiol was positively associated with the frequency of alcohol consumption (b=0.01, p=1,96×10–8), fluid intelligence (b=0.01, p=1.90×10–2) and the frequency of smoking (b=0.01, p=1.77×10–2) in males. Moreover, SHBG was associated with the frequency of alcohol consumption (b=0.01, p=2.60×10–3), fluid intelligence (b=0.01, p=4.25×10–2) and anxiety (b=-0.01, p=3.79×10–2) in females. Finally, GWGIS identified one significant loci, Tenascin R (TNR) (rs34633780, p=3.45×10–8) interacting with total testosterone for fluid intelligence.Conclusion: Our study results support the genetic effects of sex hormone on the development of intelligence and the frequency of alcohol consumption.