DNA methylation and copy number variation of the complement C4A gene in Schizophrenia

Abdull Jalil, Mohd Asyraf and Abd. Rahim, Nour El Huda and Mohd Noor, Hanisah and Harun, Noorul Amilin and A. Talib, Norlelawati (2022) DNA methylation and copy number variation of the complement C4A gene in Schizophrenia. Gene Reports, 29. ISSN 2452-0144

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Abstract

The complement gene C4A has been implicated in schizophrenia through genome-wide association studies (GWAS) and, in vitro and animal studies. However, few studies have examined epigenetic modification of the C4A gene in schizophrenia. We hypothesized that DNA methylation levels of the C4A gene are altered in schizophrenia, and the interaction between DNA methylation and the copy number (CN) of the C4A gene leads to the higher C4 levels seen in schizophrenia. In this study, C4A DNA methylation levels, C4A CN and C4 levels were measured in the peripheral blood of 183 schizophrenia cases (SZ) and 212 healthy controls (HC). The Positive and Negative Syndrome Scale (PANSS) was used to determine the severity of psychopathology in the cases. MethyLight assay was used to measure DNA methylation levels and droplet digital polymerase chain reaction (ddPCR) was used for the calculated copy number (cCN) determination. The cCNs were also grouped into copy number variation (CNV) types: deletion, normal, and duplication. Methylation levels were measured as percentage of methylated reference (PMR) values. Both C4A PMR (rs = 0.469, p < 0.001) and C4A cCN (rs = 0.210, p < 0.001) were positively correlated with C4 levels, which in turn were higher in SZ than HC. However, we found no difference in C4A PMR values or C4A CNV types between SZ and HC. Our results suggest the potential involvement of an epigenetic modification and CNV of C4A in the upregulation of complement C4 in schizophrenia.

Item Type:	Article (Journal)
Additional Information:	50 days free access to the articles: https://authors.elsevier.com/c/1g1EN8jXWOcucs
Uncontrolled Keywords:	Complement C4A, DNA methylation, Copy number variation, Schizophrenia
Subjects:	Q Science > QH Natural history > QH426 Genetics Q Science > QR Microbiology > QR180 Immunology R Medicine > RC Internal medicine > RC321 Neuroscience. Biological psychiatry. Neuropsychiatry
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button):	Kulliyyah of Medicine > Department of Basic Medical Kulliyyah of Medicine > Department of Pathology & Lab Medicine Kulliyyah of Medicine
Depositing User:	Dr Mohd Asyraf Abdull Jalil
Date Deposited:	15 Mar 2023 13:20
Last Modified:	15 Mar 2023 13:20
URI:	http://irep.iium.edu.my/id/eprint/101531

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