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

Abstract

Objective To evaluate the genetic effects of sex hormone traits on the development of mental traits in middle-aged adults. Methods The 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. Results We 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. Conclusion Our 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.

A genome-wide association study of Chinese and English language abilities in Hong Kong Chinese children

“…Interestingly, variants in TNR have been reported to be associated with cognitive performance 49 46 . In addition, a recent study 50 revealed that TNR showed a significant interaction (at p <5e-8) with total testosterone in affecting fluid intelligence in healthy adults. In addition, a recent GWAS on ADHD identified a variant in TNR as the top association achieving genome-wide significance 51 .…”

Circulating miRNAs as Potential Biomarkers for Patient Stratification in Bipolar Disorder: A Combined Review and Data Mining Approach

“…Known EFs associated with BD can be grouped into three categories based on developmental timing; prenatal (e.g., infection during pregnancy, Vitamin D levels); childhood (e.g., maltreatment, parental loss), and adolescence/adulthood (e.g., cannabis and stressful life events) [ 12 , 16 , 17 ]. While GxE have been investigated on a genome-wide scale in genome-wide gene–environment interaction studies for a number of psychiatric phenotypes [ 18 , 19 , 20 , 21 , 22 , 23 ], studies of GxE in BD have, with a few exceptions, been limited to candidate gene approaches (e.g. : variation in BDNF , stressful life event, and worst episodes of depression and mania [ 24 ], childhood trauma and age of BD onset, severity, and chronicity [ 25 ]) and a handful of other GxE associations [ 26 , 27 , 28 , 29 , 30 , 31 ]—recently reviewed by Misiak et al [ 32 ] and Musci et al [ 33 ]).…”