Investigating the shared genetic architecture between schizophrenia and sex hormone traits.

IF 5.8 1区医学 Q1 PSYCHIATRY Translational Psychiatry Pub Date : 2025-03-17 DOI:10.1038/s41398-025-03305-7

Xiaoyan He, Qingyan Ma, Jing Liu, Pu Lei, Huan Peng, Wen Lu, Yixin Liu, Xianyan Zhan, Bin Yan, Xiancang Ma, Jian Yang

{"title":"Investigating the shared genetic architecture between schizophrenia and sex hormone traits.","authors":"Xiaoyan He, Qingyan Ma, Jing Liu, Pu Lei, Huan Peng, Wen Lu, Yixin Liu, Xianyan Zhan, Bin Yan, Xiancang Ma, Jian Yang","doi":"10.1038/s41398-025-03305-7","DOIUrl":null,"url":null,"abstract":"<p><p>Sex hormones are involved in schizophrenia pathogenesis; however, their direction and genetic overlap remain unknown. By leveraging summary statistics from large-scale genome-wide association studies, we quantified the shared genetic architecture between schizophrenia and four sex hormone traits. Linkage disequilibrium score regression and bivariate causal mixture modeling strategies showed significant positive correlations between sex hormone-binding globulin (SHBG), total testosterone, and schizophrenia, while bioavailable testosterone and schizophrenia were negatively correlated. Estradiol showed a weak positive correlation with schizophrenia, with little polygenic overlap. The conjunctional false discovery rate method identified 303 lead single-nucleotide polymorphisms (SNPs) in jointly shared genomic loci between schizophrenia and SHBG, with 130, 52, and 9 SNPs shared between schizophrenia and total testosterone, bioavailable testosterone, and estradiol, respectively. Functional annotation suggests that mitotic sister chromatid segregation and N-glycan biosynthesis may be involved in common mechanisms underlying sex hormone regulation and schizophrenia onset. In conclusion, this study clarified the inherent relationships between schizophrenia and sex hormone traits, highlighted the roles of mitotic sister chromatid segregation and N-glycan biosynthesis in the pathogenesis of schizophrenia, and delivered potential targets for further validation.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"83"},"PeriodicalIF":5.8000,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational Psychiatry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41398-025-03305-7","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PSYCHIATRY","Score":null,"Total":0}

引用次数: 0

Abstract

Sex hormones are involved in schizophrenia pathogenesis; however, their direction and genetic overlap remain unknown. By leveraging summary statistics from large-scale genome-wide association studies, we quantified the shared genetic architecture between schizophrenia and four sex hormone traits. Linkage disequilibrium score regression and bivariate causal mixture modeling strategies showed significant positive correlations between sex hormone-binding globulin (SHBG), total testosterone, and schizophrenia, while bioavailable testosterone and schizophrenia were negatively correlated. Estradiol showed a weak positive correlation with schizophrenia, with little polygenic overlap. The conjunctional false discovery rate method identified 303 lead single-nucleotide polymorphisms (SNPs) in jointly shared genomic loci between schizophrenia and SHBG, with 130, 52, and 9 SNPs shared between schizophrenia and total testosterone, bioavailable testosterone, and estradiol, respectively. Functional annotation suggests that mitotic sister chromatid segregation and N-glycan biosynthesis may be involved in common mechanisms underlying sex hormone regulation and schizophrenia onset. In conclusion, this study clarified the inherent relationships between schizophrenia and sex hormone traits, highlighted the roles of mitotic sister chromatid segregation and N-glycan biosynthesis in the pathogenesis of schizophrenia, and delivered potential targets for further validation.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

性激素与精神分裂症的发病机制有关；然而，它们的作用方向和遗传重叠仍然未知。通过利用大规模全基因组关联研究的汇总统计，我们量化了精神分裂症与四种性激素性状之间的共享遗传结构。连锁不平衡得分回归和双变量因果混合建模策略显示，性激素结合球蛋白（SHBG）、总睾酮与精神分裂症之间存在显著的正相关，而生物可用睾酮与精神分裂症之间呈负相关。雌二醇与精神分裂症呈弱正相关，多基因重叠很少。共轭假发现率法在精神分裂症与SHBG之间共同共享的基因组位点上发现了303个前导单核苷酸多态性（SNPs），精神分裂症与总睾酮、生物可用睾酮和雌二醇之间分别共享130、52和9个SNPs。功能注释表明，有丝分裂姐妹染色单体分离和N-糖生物合成可能参与了性激素调控和精神分裂症发病的共同机制。总之，这项研究阐明了精神分裂症与性激素性状之间的内在关系，强调了有丝分裂姐妹染色单体分离和N-糖生物合成在精神分裂症发病机制中的作用，并提出了有待进一步验证的潜在靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Translational Psychiatry PSYCHIATRY-

CiteScore

11.50

自引率

2.90%

发文量

484

审稿时长

23 weeks

期刊介绍： Psychiatry has suffered tremendously by the limited translational pipeline. Nobel laureate Julius Axelrod''s discovery in 1961 of monoamine reuptake by pre-synaptic neurons still forms the basis of contemporary antidepressant treatment. There is a grievous gap between the explosion of knowledge in neuroscience and conceptually novel treatments for our patients. Translational Psychiatry bridges this gap by fostering and highlighting the pathway from discovery to clinical applications, healthcare and global health. We view translation broadly as the full spectrum of work that marks the pathway from discovery to global health, inclusive. The steps of translation that are within the scope of Translational Psychiatry include (i) fundamental discovery, (ii) bench to bedside, (iii) bedside to clinical applications (clinical trials), (iv) translation to policy and health care guidelines, (v) assessment of health policy and usage, and (vi) global health. All areas of medical research, including — but not restricted to — molecular biology, genetics, pharmacology, imaging and epidemiology are welcome as they contribute to enhance the field of translational psychiatry.