{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:37:03Z","timestamp":1787027823618,"version":"build-2736575974"},"reference-count":39,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,8,30]],"date-time":"2022-08-30T00:00:00Z","timestamp":1661817600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"DBT-RGCB"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The immune system seems to play a significant role in the development of schizophrenia. This becomes more evident with the emerging role of MHC complex and cytokines in schizophrenia. In the recent past, several GWAS have implied that the 6p21 region was associated with schizophrenia. However, the majority of these studies were performed in European populations. Considering tremendous variations in this region and the probability of South Indian populations being quite different from the European gene-pool from an immunogenetic point, the present study was initiated to screen SNPs in the 2.28 MB region, spanning the extended MHC locus, in 492 cases and controls from a South Indian population. We found a very strong association of rs3815087 with schizophrenia at both allelic and genotypic levels with a 7.3-fold increased risk in the recessive model. Interestingly, the association of none of the earlier reported GWAS hits, such as rs3130375, rs3131296, rs9272219, or rs3130297 were found to be replicable in our study population. rs3815087 lies in the 5\u2032UTR region of the psoriasis susceptibility 1 candidate 1 (PSORS1C1) gene, which further suggests that inflammatory processes might be an important common pathogenic pathway leading to both schizophrenia and psoriasis. The study hints at ethnic specific gene\u2013environment interaction in determining the critical threshold for disease initiation and progression.<\/jats:p>","DOI":"10.3390\/cells11172695","type":"journal-article","created":{"date-parts":[[2022,8,30]],"date-time":"2022-08-30T01:37:55Z","timestamp":1661823475000},"page":"2695","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Contribution from MHC-Mediated Risk in Schizophrenia Can Reflect a More Ethnic-Specific Genetic and Comorbid Background"],"prefix":"10.3390","volume":"11","author":[{"given":"Lekshmy","family":"Srinivas","sequence":"first","affiliation":[{"name":"Human Molecular Genetics Laboratory, Rajiv Gandhi Centre for Biotechnology, Trivandrum 695014, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neetha N.","family":"Vellichirammal","sequence":"additional","affiliation":[{"name":"Human Molecular Genetics Laboratory, Rajiv Gandhi Centre for Biotechnology, Trivandrum 695014, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Indu V.","family":"Nair","sequence":"additional","affiliation":[{"name":"Mental Health Centre, Trivandrum 695005, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandrasekharan M.","family":"Nair","sequence":"additional","affiliation":[{"name":"Nair\u2019s Hospital, Kerala 682304, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moinak","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Human Molecular Genetics Laboratory, Rajiv Gandhi Centre for Biotechnology, Trivandrum 695014, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1176\/appi.ajp.163.3.521","article-title":"Association of schizophrenia and autoimmune diseases: Linkage of Danish national registers","volume":"163","author":"Eaton","year":"2006","journal-title":"Am. J. Psychiatry"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1001\/archpsyc.1967.01730190003001","article-title":"Schizophrenia as an Immunologic Disorder I. Demonstration of antibrain globulins by fluorescent antibody techniques","volume":"16","author":"Heath","year":"1967","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1001\/archpsyc.1967.01730190012002","article-title":"Schizophrenia as an Immunologic Disorder II. Effects of Serum Protein Fractions on Brain Function","volume":"16","author":"Heath","year":"1967","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/0006-3223(91)90217-A","article-title":"Anticerebral antibodies in functional psychoses","volume":"29","author":"Shima","year":"1991","journal-title":"Biol. Psychiatry"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/0006-3223(89)90244-8","article-title":"Antiseptal brain antibody in IgG of schizophrenic patients","volume":"25","author":"Heath","year":"1989","journal-title":"Biol. Psychiatry"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/0920-9964(94)90004-3","article-title":"Increased prevalence of antibrain antibodies in the sera from schizophrenic patients","volume":"14","author":"Henneberg","year":"1994","journal-title":"Schizophr. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1007\/BF02918609","article-title":"Autoantibodies to brain and polynucleotides in patients with schizophrenia: A puzzle","volume":"11","author":"Teplizki","year":"1992","journal-title":"Immunol. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"257184","DOI":"10.1155\/2013\/257184","article-title":"Autoantibodies and the immune hypothesis in psychotic brain diseases: Challenges and perspectives","volume":"2013","author":"Pathmanandavel","year":"2013","journal-title":"Clin. Dev. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"131","DOI":"10.3389\/fpsyt.2019.00131","article-title":"Autoimmune Diseases and Psychotic Disorders","volume":"10","author":"Jeppesen","year":"2019","journal-title":"Front. Psychiatry"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"536257","DOI":"10.3389\/fpsyt.2021.536257","article-title":"Cytokine Imbalance in Schizophrenia. From Research to Clinic: Potential Implications for Treatment","volume":"12","author":"Reale","year":"2021","journal-title":"Front. Psychiatry"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1186\/s12974-016-0569-8","article-title":"Pro-inflammatory cytokines and their epistatic interactions in genetic susceptibility to schizophrenia","volume":"13","author":"Srinivas","year":"2016","journal-title":"J. Neuroinflamm."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1038\/nature08185","article-title":"Common polygenic variation contributes to risk of schizophrenia and bipolar disorder","volume":"460","author":"Purcell","year":"2009","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1038\/nature08192","article-title":"Common variants on chromosome 6p22.1 are associated with schizophrenia","volume":"460","author":"Shi","year":"2009","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1038\/nature08186","article-title":"Common variants conferring risk of schizophrenia","volume":"460","author":"Stefansson","year":"2009","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1038\/ng.2742","article-title":"Genome-wide association analysis identifies 13 new risk loci for schizophrenia","volume":"45","author":"Ripke","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1017\/S0033291700034036","article-title":"Is schizophrenia an HLA-associated disease?","volume":"9","author":"McGuffin","year":"1979","journal-title":"Psychol. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/s40473-018-0155-8","article-title":"The MHC\/HLA gene complex in major psychiatric disorders: Emerging roles and implications","volume":"5","author":"Debnath","year":"2018","journal-title":"Curr. Behav. Neurosci. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"112","DOI":"10.3109\/13651501.2010.533181","article-title":"HLA-DRB1 association with schizophrenia in Saudi Arabian patients","volume":"15","author":"Kadasah","year":"2011","journal-title":"Int. J. Psychiatry Clin. Pract."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1176\/ajp.153.12.1530","article-title":"Genetic association of the HLA DRB1 gene locus on chromosome 6p21.3 with schizophrenia","volume":"153","author":"Wright","year":"1996","journal-title":"Am. J. Psychiatry"},{"key":"ref_20","first-page":"225","article-title":"A crypto-Dravidian origin for the nontribal communities of South India based on human leukocyte antigen class I diversity","volume":"68","author":"Thomas","year":"2006","journal-title":"HLA"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Saradalekshmi, K.R., Neetha, N.V., Sathyan, S., Nair, I.V., Nair, C.M., and Banerjee, M. (2014). DNA methyl transferase (DNMT) gene polymorphisms could be a primary event in epigenetic susceptibility to schizophrenia. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0098182"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1038\/78044","article-title":"The NOTCH4 locus is associated with susceptibility to schizophrenia","volume":"25","author":"Wei","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1186\/gb-2009-10-9-236","article-title":"Common variants in polygenic schizophrenia","volume":"10","author":"Glessner","year":"2009","journal-title":"Genome. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1046\/j.1523-1747.2002.19612.x","article-title":"Evidence for a major psoriasis susceptibility locus at 6p21 (PSORS1) and a novel candidate region at 4q31 by genome-wide scan in Chinese Hans","volume":"119","author":"Hang","year":"2002","journal-title":"J. Investig. Dermatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1111\/j.1365-2133.2006.07420.x","article-title":"Psoriasis vulgaris in Chinese individuals is associated with PSORS1C3 and CDSN genes","volume":"155","author":"Chang","year":"2006","journal-title":"Br. J. Dermatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/S0920-9964(99)00066-3","article-title":"Schizophrenia associated with psoriasis vulgaris: Three case reports","volume":"41","author":"Miyaoka","year":"2000","journal-title":"Schizophr. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1111\/j.1365-2133.2011.10684.x","article-title":"Increased Risk of Psoriasis among Patients with Schizophrenia: A Nationwide Population-based Study","volume":"166","author":"Yang","year":"2012","journal-title":"Brit. J. Dermatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"141","DOI":"10.4103\/jpgm.JPGM_253_18","article-title":"Patients with psoriasis have a higher risk of schizophrenia: A systematic review and meta-analysis of observational studies","volume":"65","author":"Ungprasert","year":"2019","journal-title":"J. Postgrad. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/S0920-9964(03)00017-3","article-title":"Rheumatoid arthritis and schizophrenia: A negative association at a dimensional level","volume":"66","author":"Gorwood","year":"2004","journal-title":"Schizophr. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1093\/schbul\/sbu054","article-title":"The association between schizophrenia and rheumatoid arthritis: A nationwide population-based Swedish study on intraindividual and familial risks","volume":"40","author":"Sellgren","year":"2014","journal-title":"Schizophr. Bull."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1002\/ajmg.b.32282","article-title":"The relationship between schizophrenia and rheumatoid arthritis revisited: Genetic and epidemiological analyses","volume":"168","author":"Euesden","year":"2015","journal-title":"Am. J. Med. Genet. Part B Neuropsychiatr. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1056\/NEJMoa073491","article-title":"TRAF1\u2013C5 as a risk locus for rheumatoid arthritis\u2014A genomewide study","volume":"357","author":"Plenge","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/s41398-022-01811-6","article-title":"Immune marker levels in severe mental disorders: Associations with polygenic risk scores of related mental phenotypes and psoriasis","volume":"12","author":"Werner","year":"2022","journal-title":"Transl. Psychiatry"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"100330","DOI":"10.1016\/j.bbih.2021.100330","article-title":"T regulatory cells as a potential therapeutic target in psychosis? Current challenges and future perspectives","volume":"17","author":"Deakin","year":"2021","journal-title":"Brain Behav. Immun. Health"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S0162-3109(97)00037-4","article-title":"Short- and long-term immunosuppressive effects of clozapine and haloperidol","volume":"37","author":"Leykin","year":"1997","journal-title":"Immunopharmacology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/S0920-9964(99)00116-4","article-title":"Immunosuppressive effects of clozapine and haloperidol: Enhanced production of the interleukin-1 receptor antagonist","volume":"42","author":"Song","year":"2000","journal-title":"Schizophr. Res."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Bujor, C.E., Vang, T., Nielsen, J., and Schjerning, O. (2017). Antipsychotic-associated psoriatic rash\u2014A case report. BMC Psych., 17.","DOI":"10.1186\/s12888-017-1411-2"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1159\/000119379","article-title":"Side effect profile of azathioprine in the treatment of chronic schizophrenic patients","volume":"36","author":"Levine","year":"1997","journal-title":"Neuropsychobiology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.psychres.2018.09.006","article-title":"Increased circulating regulatory T cells in medicated people with schizophrenia","volume":"269","author":"Kelly","year":"2018","journal-title":"Psychiatry Res."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/17\/2695\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:19:57Z","timestamp":1760141997000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/17\/2695"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,30]]},"references-count":39,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["cells11172695"],"URL":"https:\/\/doi.org\/10.3390\/cells11172695","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,30]]}}}