评估性激素特征对精神特征发育的遗传影响：英国生物库队列的多基因评分分析和基因-环境广泛相互作用研究。
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.
机构信息
National Local Joint Engineering Research Center of Biodiagnostics and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, 71006, China.
出版信息
Mol Brain. 2021 Jan 6;14(1):3. doi: 10.1186/s13041-020-00718-x.
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) 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) in middle-aged males. Moreover, bioavailable testosterone was associated with the fluid intelligence (b = - 0.0136, p = 5.74 × 10) in middle-aged females. Finally, GEWIS identified one significant loci, Tenascin R (TNR) (rs34633780, p = 3.45 × 10) 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.
目的
评估性激素特征对中年成年人心理特征发展的遗传影响。
方法
与性激素特征相关的 SNP 源自两阶段全基因组关联研究 (GWAS)。本研究选择了四种性激素特征，包括性激素结合球蛋白 (SHBG)、睾酮、生物可利用睾酮和雌二醇。个体水平基因型数据来自英国生物样本库 (UK Biobank) 队列的多基因风险评分 (PRS)。然后，我们使用逻辑和线性回归模型评估个体性激素特征 PRS 与饮酒频率、焦虑、智力等之间的关联。最后，通过 PLINK2.0 进行基因-环境广泛相互作用研究 (GEWIS)，以检测与 SHBG 和雌二醇等性激素特征在流动智力和吸烟、饮酒频率发展中相互作用的新候选基因。
结果
我们观察到 SHBG 与中年男性和女性饮酒频率呈正相关 (b=0.0101, p=3.84×10)。此外，雌二醇与中年男性饮酒频率呈正相关 (b=0.0128, p=1.96×10)。此外，生物可利用睾酮与中年女性的流动智力呈负相关 (b=-0.0136, p=5.74×10)。最后，GEWIS 确定了一个显著的位点，Tenascin R (TNR) (rs34633780, p=3.45×10)，它与总睾酮相互作用，影响流动智力。
结论
我们的研究结果支持性激素特征对英国中年成年人智力和饮酒频率发展的遗传影响。
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