The genetic overlap between schizophrenia and major depression with cognitive function.

IF 10.4 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Psychiatry Pub Date : 2026-09-16 DOI:10.1038/s41380-026-03887-8

Qiao Su, Meijuan Li, Yuying Qiu, Xiaoxiao Sun, Zhenning Feng, Ying Xu, Boxuan Zhou, Jie Li

{"title":"The genetic overlap between schizophrenia and major depression with cognitive function.","authors":"Qiao Su, Meijuan Li, Yuying Qiu, Xiaoxiao Sun, Zhenning Feng, Ying Xu, Boxuan Zhou, Jie Li","doi":"10.1038/s41380-026-03887-8","DOIUrl":null,"url":null,"abstract":"<p><p>This study aimed to systematically dissect the shared genetic basis of schizophrenia (SCZ) and major depression (MD) with cognitive function. To investigate this, we integrated large-scale genome-wide association studies (GWAS) summary statistics for SCZ (N = 175,799, [cases, 74,776; controls, 101,023]), MD (N = 2,622,273 [cases, 550,355; controls, 2,071,918]) and four cognitive traits (reaction time, N = 330,069; memory, N = 112,067; verbal-numerical reasoning, N = 36,035; educational attainment, N = 111,114). Linkage disequilibrium (LD) score regression analysis revealed that SCZ showed significant negative genetic correlations with reaction time, memory, and verbal-numerical reasoning. MD showed negative genetic correlations with memory, verbal-numerical reasoning, and educational attainment. Bayesian colocalization analysis identified seven genomic regions with strong or supportive evidence between SCZ and cognitive function, and two genomic regions with supportive evidence between MD and cognitive function. Gene mapping and over representation analysis (ORA) indicated that SCZ-associated genes were primarily involved in pathways related to transport processes, and MD-associated genes were significantly enriched in pathways related to neural development. Through genetic correlation and colocalization analysis, this study elucidates the genetic overlap between SCZ and MD with cognitive function, providing a new perspective for related research.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":" ","pages":""},"PeriodicalIF":10.4000,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Psychiatry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41380-026-03887-8","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

This study aimed to systematically dissect the shared genetic basis of schizophrenia (SCZ) and major depression (MD) with cognitive function. To investigate this, we integrated large-scale genome-wide association studies (GWAS) summary statistics for SCZ (N = 175,799, [cases, 74,776; controls, 101,023]), MD (N = 2,622,273 [cases, 550,355; controls, 2,071,918]) and four cognitive traits (reaction time, N = 330,069; memory, N = 112,067; verbal-numerical reasoning, N = 36,035; educational attainment, N = 111,114). Linkage disequilibrium (LD) score regression analysis revealed that SCZ showed significant negative genetic correlations with reaction time, memory, and verbal-numerical reasoning. MD showed negative genetic correlations with memory, verbal-numerical reasoning, and educational attainment. Bayesian colocalization analysis identified seven genomic regions with strong or supportive evidence between SCZ and cognitive function, and two genomic regions with supportive evidence between MD and cognitive function. Gene mapping and over representation analysis (ORA) indicated that SCZ-associated genes were primarily involved in pathways related to transport processes, and MD-associated genes were significantly enriched in pathways related to neural development. Through genetic correlation and colocalization analysis, this study elucidates the genetic overlap between SCZ and MD with cognitive function, providing a new perspective for related research.

Abstract Image

查看原文本刊更多论文

精神分裂症和重度抑郁症与认知功能的基因重叠。

本研究旨在系统剖析具有认知功能的精神分裂症（SCZ）和重度抑郁症（MD）的共同遗传基础。为了研究这一点，我们整合了大规模全基因组关联研究（GWAS）对SCZ （N = 175,799，[病例，74,776；对照组，101,023]）、MD （N = 2,622,273[病例，550,355；对照组，2,071,918]）和四个认知特征（反应时间，N = 330,069；记忆力，N = 112,067；语言-数字推理，N = 36,035；受教育程度，N = 111,114）的汇总统计数据。联系不平衡（LD）得分回归分析显示，SCZ与反应时间、记忆和言语-数字推理均呈显著负相关。MD与记忆、语言-数字推理和受教育程度呈负相关。贝叶斯共定位分析发现，有7个基因组区域在SCZ和认知功能之间存在强证据或支持证据，有2个基因组区域在MD和认知功能之间存在支持证据。基因定位和过代表性分析（ORA）表明，scz相关基因主要参与转运相关通路，md相关基因在神经发育相关通路中显著富集。本研究通过遗传相关和共定位分析，阐明了SCZ和MD与认知功能之间的遗传重叠，为相关研究提供了新的视角。

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

Molecular Psychiatry 医学-精神病学

CiteScore

20.50

自引率

4.50%

发文量

459

审稿时长

4-8 weeks

期刊介绍： Molecular Psychiatry focuses on publishing research that aims to uncover the biological mechanisms behind psychiatric disorders and their treatment. The journal emphasizes studies that bridge pre-clinical and clinical research, covering cellular, molecular, integrative, clinical, imaging, and psychopharmacology levels.