{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:17:27Z","timestamp":1788999447582,"version":"build-2803163510"},"reference-count":47,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T00:00:00Z","timestamp":1690934400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["HLA"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:p>Immune dysregulation has been widely observed in patients with psychiatric disorders. This study aims to examine the association between HLA alleles and depression and anxiety. Using data from the UK Biobank, we performed regression analyses to assess the association of 359 HLA alleles with depression and anxiety, as determined by Patient Health Questionnaire (PHQ) score (<jats:italic>n<\/jats:italic>\u2009=\u2009120,033), self\u2010reported depression (<jats:italic>n<\/jats:italic>\u2009=\u2009121,685), general anxiety disorder (GAD\u20107) score (<jats:italic>n<\/jats:italic>\u2009=\u2009120,590), and self\u2010reported anxiety (<jats:italic>n<\/jats:italic>\u2009=\u2009108,310). Subsequently, we conducted gene environmental interaction study (GEIS) to evaluate the potential effects of interactions between HLA alleles and environmental factors on the risk of depression and anxiety. Sex stratification was implemented in all analysis. Our study identified two significant HLA alleles associated with self\u2010reported depression, including <jats:italic>HLA\u2010C*07:01<\/jats:italic> (<jats:italic>\u03b2<\/jats:italic>\u2009=\u2009\u22120.015, <jats:italic>p<\/jats:italic>\u2009=\u20095.54\u2009\u00d7\u200910<jats:sup>\u22125<\/jats:sup>) and <jats:italic>HLA\u2010B*08:01<\/jats:italic> (<jats:italic>\u03b2<\/jats:italic>\u2009=\u2009\u22120.015, <jats:italic>p<\/jats:italic>\u2009=\u20097.78\u2009\u00d7\u200910<jats:sup>\u22125<\/jats:sup>). Additionally, we identified four significant HLA alleles associated with anxiety score, such as <jats:italic>HLA\u2010DRB1*07:01<\/jats:italic> (<jats:italic>\u03b2<\/jats:italic>\u2009=\u20090.084, <jats:italic>p<\/jats:italic>\u2009=\u20099.28\u2009\u00d7\u200910<jats:sup>\u22125<\/jats:sup>) and <jats:italic>HLA\u2010B*57:01<\/jats:italic> (<jats:italic>\u03b2<\/jats:italic>\u2009=\u20090.139, <jats:italic>p<\/jats:italic>\u2009=\u20091.22\u2009\u00d7\u200910<jats:sup>\u22124<\/jats:sup>). GEIS revealed that certain HLA alleles interacted with environmental factors to influence mental health outcomes. For instance, <jats:italic>HLA\u2010A*02:07<\/jats:italic>\u2009\u00d7\u2009cigarette smoking was associated with depression score (<jats:italic>\u03b2<\/jats:italic>\u2009=\u20090.976, <jats:italic>p<\/jats:italic>\u2009=\u20091.88\u2009\u00d7\u200910<jats:sup>\u22126<\/jats:sup>). Moreover, sex stratification analysis revealed significant sex\u2010based differences in the interaction effects of certain HLA alleles with environmental factors. Our findings indicate the considerable impact of HLA alleles on the risks of depression and anxiety, providing valuable insights into the functional relevance of immune dysfunction in these conditions.<\/jats:p>","DOI":"10.1111\/tan.15173","type":"journal-article","created":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T09:30:23Z","timestamp":1690968623000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Associations of classical <scp>HLA<\/scp> alleles with depression and anxiety"],"prefix":"10.1111","volume":"103","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2915-5535","authenticated-orcid":false,"given":"Bolun","family":"Cheng","sequence":"first","affiliation":[{"name":"Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education of China, Collaborative Innovation Center of Endemic Disease and Health Promotion for Silk Road Region, School of Public Health, Health Science Center Xi'an Jiaotong University  Xi'an People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Yang","sequence":"additional","affiliation":[{"name":"Clinical Research Center The First Affiliated Hospital of Xi'an Jiaotong University  Xi'an People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiqiang","family":"Cheng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education of China, Collaborative Innovation Center of Endemic Disease and Health Promotion for Silk Road Region, School of Public Health, Health Science Center Xi'an Jiaotong University  Xi'an People's Republic of 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