Journal
WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY
Volume 23, Issue 3, Pages 208-218Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/15622975.2021.1939155
Keywords
White matter; oligodendrocyte; myelin; schizophrenia; autism spectrum disorders; gene-gene interaction
Categories
Funding
- Eranet Neuron Consortium AUSZ: from Autism to SchiZophrenia: study of the genetic mechanisms underlying brain dysfunction and structural phenotypes in schizophrenia and autistic spectrum disorders [ANR-2010-NEUR-002-01, PIM2010ERN-00642]
- Fondation de France [GDR 3557, 15142]
- Comissionat per a Universitats i Recerca del DIUE of the Generalitat de Catalunya (Agencia de Gestio d'Ajuts Universitaris i de Recerca (AGAUR) [2017SGR1577, 2017SGR1271]
- Ajuts de Personal Investigador Predoctoral en Formacio (APIF-IBUB-Universitat de Barcelona)
- Spanish Ministry of Economy and Competitivity, Instituto de Salud Carlos III [PI18/01535]
- Miguel Servet contract [CP20/00072]
- European Regional Development Fund (ERDF)/European Social Fund Investing in your future
- Aarhus University graduate school
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This study investigated the role of oligodendrocyte/myelin-related genes in schizophrenia-spectrum disorders (SSD) and Autism spectrum disorders (ASD), finding associations with genes like MBP, ERBB3, and AKT1. Significant gene-gene interactions were also identified, suggesting potential pathophysiological mechanisms related to NRG1/ERBBs signaling in these disorders.
Background Schizophrenia-spectrum disorders (SSD) and Autism spectrum disorders (ASD) are neurodevelopmental disorders that share clinical, cognitive, and genetic characteristics, as well as particular white matter (WM) abnormalities. In this study, we aimed to investigate the role of a set of oligodendrocyte/myelin-related (OMR) genes and their epistatic effect on the risk for SSD and ASD. Methods We examined 108 SNPs in a set of 22 OMR genes in 1749 subjects divided into three independent samples (187 SSD trios, 915 SSD cases/control, and 91 ASD trios). Genetic association and gene-gene interaction analyses were conducted with PLINK and MB-MDR, and permutation procedures were implemented in both. Results Some OMR genes showed an association trend with SSD, while after correction, the ones that remained significantly associated were MBP, ERBB3, and AKT1. Significant gene-gene interactions were found between (i) NRG1*MBP (perm p-value = 0.002) in the SSD trios sample, (ii) ERBB3*AKT1 (perm p-value = 0.001) in the SSD case-control sample, and (iii) ERBB3*QKI (perm p-value = 0.0006) in the ASD trios sample. Discussion Our results suggest the implication of OMR genes in the risk for both SSD and ASD and highlight the role of NRG1 and ERBB genes. These findings are in line with the previous evidence and may suggest pathophysiological mechanisms related to NRG1/ERBBs signalling in these disorders.
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