Dissecting the genetic interaction between breast cancer risk and schizophrenia: evidence from crosstrait genome-wide analysis.

IF 1.4 4区医学 Q4 GENETICS & HEREDITY

Psychiatric Genetics Pub Date : 2026-03-01 Epub Date: 2025-12-09 DOI:10.1097/YPG.0000000000000410

Min Zhang, Yongli Wu, Yujie Qin

{"title":"Dissecting the genetic interaction between breast cancer risk and schizophrenia: evidence from crosstrait genome-wide analysis.","authors":"Min Zhang, Yongli Wu, Yujie Qin","doi":"10.1097/YPG.0000000000000410","DOIUrl":null,"url":null,"abstract":"Background: Epidemiological evidence suggests a link between schizophrenia (SCZ) and increased breast cancer (BC) risk, but the genetic mechanisms remain unclear. Exploring their shared genetic susceptibility may help reveal the basis of this comorbidity.Methods: This study was conducted utilizing genome-wide association study (GWAS) data for SCZ and BC, employing a multitiered genetic analytical framework to systematically assess the genetic association patterns between these two conditions. Initially, linkage disequilibrium score regression and high-dimensional likelihood modeling were applied to quantitatively evaluate genome-wide genetic correlations, while localized variant association analysis was performed to detect regional genetic association signals within specific genomic loci. Subsequently, conditional/conjunctional false discovery rate (condFDR/conjFDR) methodologies were implemented to uncover the shared genetic architecture underlying both traits. Ultimately, conjFDR was integrated with multitrait analysis of GWAS (MTAG) strategies to further identify and validate potentially overlapping genetic variant loci.Results: The analysis revealed significantly positive genome-wide genetic correlations between SCZ and BC, as well as among various BC subtypes. Regional genetic structure analysis identified numerous chromosomal loci exhibiting shared genetic signals. The condFDR/conjFDR models provided additional confirmation of the genetic overlap between the two traits. Through the combined application of conjFDR and MTAG, a collection of shared genetic loci with plausible biological relevance was identified and substantiated, including BATXN7, FOXP1, EMB, LINC00536, ZNF365, MAPT, STXBP4 , and GATAD2A .Conclusion: The findings elucidated genetic associations between SCZ and BC and identified critical shared genetic contributors, thereby offering molecular evidence for the investigation of comorbidity mechanisms and potential intervention strategies.","PeriodicalId":20734,"journal":{"name":"Psychiatric Genetics","volume":" ","pages":"32-41"},"PeriodicalIF":1.4000,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Psychiatric Genetics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/YPG.0000000000000410","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/12/9 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Epidemiological evidence suggests a link between schizophrenia (SCZ) and increased breast cancer (BC) risk, but the genetic mechanisms remain unclear. Exploring their shared genetic susceptibility may help reveal the basis of this comorbidity.

Methods: This study was conducted utilizing genome-wide association study (GWAS) data for SCZ and BC, employing a multitiered genetic analytical framework to systematically assess the genetic association patterns between these two conditions. Initially, linkage disequilibrium score regression and high-dimensional likelihood modeling were applied to quantitatively evaluate genome-wide genetic correlations, while localized variant association analysis was performed to detect regional genetic association signals within specific genomic loci. Subsequently, conditional/conjunctional false discovery rate (condFDR/conjFDR) methodologies were implemented to uncover the shared genetic architecture underlying both traits. Ultimately, conjFDR was integrated with multitrait analysis of GWAS (MTAG) strategies to further identify and validate potentially overlapping genetic variant loci.

Results: The analysis revealed significantly positive genome-wide genetic correlations between SCZ and BC, as well as among various BC subtypes. Regional genetic structure analysis identified numerous chromosomal loci exhibiting shared genetic signals. The condFDR/conjFDR models provided additional confirmation of the genetic overlap between the two traits. Through the combined application of conjFDR and MTAG, a collection of shared genetic loci with plausible biological relevance was identified and substantiated, including BATXN7, FOXP1, EMB, LINC00536, ZNF365, MAPT, STXBP4 , and GATAD2A .

Conclusion: The findings elucidated genetic associations between SCZ and BC and identified critical shared genetic contributors, thereby offering molecular evidence for the investigation of comorbidity mechanisms and potential intervention strategies.

查看原文本刊更多论文

剖析乳腺癌风险与精神分裂症之间的遗传相互作用：来自海峡两岸全基因组分析的证据。

背景：流行病学证据表明精神分裂症（SCZ）与乳腺癌（BC）风险增加之间存在联系，但遗传机制尚不清楚。探索他们共同的遗传易感性可能有助于揭示这种共病的基础。方法：本研究利用SCZ和BC的全基因组关联研究（GWAS）数据，采用多层遗传分析框架系统评估这两种疾病之间的遗传关联模式。最初，我们采用连锁不平衡评分回归和高维似然模型来定量评估全基因组遗传相关性，而局部变异关联分析则用于检测特定基因组位点内的区域遗传关联信号。随后，实施了条件/联合错误发现率（condFDR/ condFDR）方法来揭示这两个特征背后的共享遗传结构。最后，结合多性状分析的GWAS （MTAG）策略，进一步鉴定和验证可能重叠的遗传变异位点。结果：分析显示SCZ与BC以及各种BC亚型之间存在显著的全基因组正相关。区域遗传结构分析发现了许多具有共享遗传信号的染色体位点。condFDR/ conjufdr模型进一步证实了这两个性状之间的遗传重叠。通过联合应用conjufdr和MTAG，鉴定并证实了一系列具有生物学相关性的共享基因位点，包括BATXN7、FOXP1、EMB、LINC00536、ZNF365、MAPT、STXBP4和GATAD2A。结论：研究结果阐明了SCZ和BC之间的遗传关联，并确定了关键的共享遗传因子，从而为研究合并症机制和潜在的干预策略提供了分子证据。

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分钟内获得全文求助全文

来源期刊

Psychiatric Genetics 医学-神经科学

CiteScore

2.30

自引率

0.00%

发文量

审稿时长

3 months

期刊介绍： The journal aims to publish papers which bring together clinical observations, psychological and behavioural abnormalities and genetic data. All papers are fully refereed. Psychiatric Genetics is also a forum for reporting new approaches to genetic research in psychiatry and neurology utilizing novel techniques or methodologies. Psychiatric Genetics publishes original Research Reports dealing with inherited factors involved in psychiatric and neurological disorders. This encompasses gene localization and chromosome markers, changes in neuronal gene expression related to psychiatric disease, linkage genetics analyses, family, twin and adoption studies, and genetically based animal models of neuropsychiatric disease. The journal covers areas such as molecular neurobiology and molecular genetics relevant to mental illness. Reviews of the literature and Commentaries in areas of current interest will be considered for publication. Reviews and Commentaries in areas outside psychiatric genetics, but of interest and importance to Psychiatric Genetics, will also be considered. Psychiatric Genetics also publishes Book Reviews, Brief Reports and Conference Reports.