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Contribution from MHC-Mediated Risk in Schizophrenia Can Reflect a More Ethnic-Specific Genetic and Comorbid Background

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 m...

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Autores principales: Srinivas, Lekshmy, Vellichirammal, Neetha N., Nair, Indu V., Nair, Chandrasekharan M., Banerjee, Moinak
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9454640/
https://www.ncbi.nlm.nih.gov/pubmed/36078103
http://dx.doi.org/10.3390/cells11172695
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author Srinivas, Lekshmy
Vellichirammal, Neetha N.
Nair, Indu V.
Nair, Chandrasekharan M.
Banerjee, Moinak
author_facet Srinivas, Lekshmy
Vellichirammal, Neetha N.
Nair, Indu V.
Nair, Chandrasekharan M.
Banerjee, Moinak
author_sort Srinivas, Lekshmy
collection PubMed
description 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′UTR 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–environment interaction in determining the critical threshold for disease initiation and progression.
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spelling pubmed-94546402022-09-09 Contribution from MHC-Mediated Risk in Schizophrenia Can Reflect a More Ethnic-Specific Genetic and Comorbid Background Srinivas, Lekshmy Vellichirammal, Neetha N. Nair, Indu V. Nair, Chandrasekharan M. Banerjee, Moinak Cells Article 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′UTR 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–environment interaction in determining the critical threshold for disease initiation and progression. MDPI 2022-08-30 /pmc/articles/PMC9454640/ /pubmed/36078103 http://dx.doi.org/10.3390/cells11172695 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Srinivas, Lekshmy
Vellichirammal, Neetha N.
Nair, Indu V.
Nair, Chandrasekharan M.
Banerjee, Moinak
Contribution from MHC-Mediated Risk in Schizophrenia Can Reflect a More Ethnic-Specific Genetic and Comorbid Background
title Contribution from MHC-Mediated Risk in Schizophrenia Can Reflect a More Ethnic-Specific Genetic and Comorbid Background
title_full Contribution from MHC-Mediated Risk in Schizophrenia Can Reflect a More Ethnic-Specific Genetic and Comorbid Background
title_fullStr Contribution from MHC-Mediated Risk in Schizophrenia Can Reflect a More Ethnic-Specific Genetic and Comorbid Background
title_full_unstemmed Contribution from MHC-Mediated Risk in Schizophrenia Can Reflect a More Ethnic-Specific Genetic and Comorbid Background
title_short Contribution from MHC-Mediated Risk in Schizophrenia Can Reflect a More Ethnic-Specific Genetic and Comorbid Background
title_sort contribution from mhc-mediated risk in schizophrenia can reflect a more ethnic-specific genetic and comorbid background
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9454640/
https://www.ncbi.nlm.nih.gov/pubmed/36078103
http://dx.doi.org/10.3390/cells11172695
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