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...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-08-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/11/17/2695 |
| _version_ | 1797495934684233728 |
|---|---|
| author | Lekshmy Srinivas Neetha N. Vellichirammal Indu V. Nair Chandrasekharan M. Nair Moinak Banerjee |
| author_facet | Lekshmy Srinivas Neetha N. Vellichirammal Indu V. Nair Chandrasekharan M. Nair Moinak Banerjee |
| author_sort | Lekshmy Srinivas |
| collection | DOAJ |
| 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 (<i>PSORS1C1</i>) 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. |
| first_indexed | 2024-03-10T01:56:37Z |
| format | Article |
| id | doaj.art-2526619c16d34a37bd6aa596024908ca |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T01:56:37Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-2526619c16d34a37bd6aa596024908ca2023-11-23T12:55:23ZengMDPI AGCells2073-44092022-08-011117269510.3390/cells11172695Contribution from MHC-Mediated Risk in Schizophrenia Can Reflect a More Ethnic-Specific Genetic and Comorbid BackgroundLekshmy Srinivas0Neetha N. Vellichirammal1Indu V. Nair2Chandrasekharan M. Nair3Moinak Banerjee4Human Molecular Genetics Laboratory, Rajiv Gandhi Centre for Biotechnology, Trivandrum 695014, IndiaHuman Molecular Genetics Laboratory, Rajiv Gandhi Centre for Biotechnology, Trivandrum 695014, IndiaMental Health Centre, Trivandrum 695005, IndiaNair’s Hospital, Kerala 682304, IndiaHuman Molecular Genetics Laboratory, Rajiv Gandhi Centre for Biotechnology, Trivandrum 695014, IndiaThe 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 (<i>PSORS1C1</i>) 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.https://www.mdpi.com/2073-4409/11/17/2695schizophreniaMHCSNPsimmune systemenvironmentpsoriasis |
| spellingShingle | Lekshmy Srinivas Neetha N. Vellichirammal Indu V. Nair Chandrasekharan M. Nair Moinak Banerjee Contribution from MHC-Mediated Risk in Schizophrenia Can Reflect a More Ethnic-Specific Genetic and Comorbid Background Cells schizophrenia MHC SNPs immune system environment psoriasis |
| 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 | schizophrenia MHC SNPs immune system environment psoriasis |
| url | https://www.mdpi.com/2073-4409/11/17/2695 |
| work_keys_str_mv | AT lekshmysrinivas contributionfrommhcmediatedriskinschizophreniacanreflectamoreethnicspecificgeneticandcomorbidbackground AT neethanvellichirammal contributionfrommhcmediatedriskinschizophreniacanreflectamoreethnicspecificgeneticandcomorbidbackground AT induvnair contributionfrommhcmediatedriskinschizophreniacanreflectamoreethnicspecificgeneticandcomorbidbackground AT chandrasekharanmnair contributionfrommhcmediatedriskinschizophreniacanreflectamoreethnicspecificgeneticandcomorbidbackground AT moinakbanerjee contributionfrommhcmediatedriskinschizophreniacanreflectamoreethnicspecificgeneticandcomorbidbackground |