Abstract
ObjectiveTo evaluate the genetic effects of sex hormone traits on the development of mental traits in middle-aged adults.MethodsThe SNPs associated with sex hormone traits were derived from a two-stage genome-wide association study (GWAS). Four sex hormone traits were selected in the current study, including sex hormone-binding globulin (SHBG), testosterone, bioavailable testosterone and estradiol. The polygenic risk score (PRS) of sex hormone traits were calculated from individual-level genotype data of the United Kingdom (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, gene-environment-wide interaction study (GEWIS) was performed to detect novel candidate genes interacting with the sex hormone traits on the development of fluid intelligence and the frequency of smoking and alcohol consumption by PLINK2.0.ResultsWe observed positive association between SHBG and the frequency of alcohol consumption (b = 0.0101, p = 3.84 × 10–11) in middle-aged males and females. In addition, estradiol was positively associated with the frequency of alcohol consumption (b = 0.0128, p = 1.96 × 10–8) in middle-aged males. Moreover, bioavailable testosterone was associated with the fluid intelligence (b = − 0.0136, p = 5.74 × 10–5) in middle-aged females. Finally, GEWIS identified one significant loci, Tenascin R (TNR) (rs34633780, p = 3.45 × 10–8) interacting with total testosterone for fluid intelligence.ConclusionOur study results support the genetic effects of sex hormone traits on the development of intelligence and the frequency of alcohol consumption in middle-aged adults in UK.
Highlights
Mental disorders are highly prevalent and disabling globally, which lead to heavy burden on the health care system and society [1]
United Kingdom (UK) Biobank samples and mental phenotypes The phenotypic and genotypic data of this study were derived from UK Biobank health resource under UK Biobank application 46478, which was a populationbased prospective cohort study
Anxiety and depression were defined according to the previous study [29], which were based on the general anxiety disorder (GAD-7) and Patient Health Questionnaire (PHQ-9) [30, 31]
Summary
Mental disorders are highly prevalent and disabling globally, which lead to heavy burden on the health care system and society [1]. Based on the Global Burden of Disease, Injuries, and Risk Factors Study 2017 (GBD 2017), mental disorders consistently accounted for more than 14% of age-standardized years lived with disability for nearly 30 years [2]. It has been reported that 17.6% of adults suffered from a common mental disorder within the past 12 months and 29.2% across their lifetime [3]. Tobacco addiction is the most common co-occurring disorder among persons with serious mental illness [6]. The intelligence is linked to the risk of whole range of mental disorders [7]
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