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Common risk alleles for schizophrenia within the major histocompatibility complex predict white matter microstructure

Caseras, Xavier ORCID:, Simmonds, Emily, Pardiñas, Antonio F. ORCID:, Anney, Richard ORCID:, Legge, Sophie E., Walters, James T. R. ORCID:, Harrison, Neil A. ORCID:, O’Donovan, Michael C. and Escott-Price, Valentina ORCID: 2024. Common risk alleles for schizophrenia within the major histocompatibility complex predict white matter microstructure. Translational Psychiatry 14 , 194. 10.1038/s41398-024-02910-2

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Recent research has highlighted the role of complement genes in shaping the microstructure of the brain during early development, and in contributing to common allele risk for Schizophrenia. We hypothesised that common risk variants for schizophrenia within complement genes will associate with structural changes in white matter microstructure within tracts innervating the frontal lobe. Results showed that risk alleles within the complement gene set, but also intergenic alleles, significantly predict axonal density in white matter tracts connecting frontal cortex with parietal, temporal and occipital cortices. Specifically, risk alleles within the Major Histocompatibility Complex region in chromosome 6 appeared to drive these associations. No significant associations were found for the orientation dispersion index. These results suggest that changes in axonal packing - but not in axonal coherence - determined by common risk alleles within the MHC genomic region – including variants related to the Complement system - appear as a potential neurobiological mechanism for schizophrenia.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Additional Information: License information from Publisher: LICENSE 1: URL:, Type: open-access
Publisher: Springer Nature
ISSN: 2158-3188
Funders: MRC
Date of First Compliant Deposit: 23 April 2024
Date of Acceptance: 12 April 2024
Last Modified: 01 Jul 2024 15:03

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