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

Autor: Caseras X; Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK. CaserasX@cardiff.ac.uk., Simmonds E; Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.; Dementia Research Institute, London, UK., Pardiñas AF; Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK., Anney R; Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK., Legge SE; Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK., Walters JTR; Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK., Harrison NA; Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.; Cardiff University Brain Research Imaging Centre, Cardiff University, Cardiff, UK., O'Donovan MC; Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK., Escott-Price V; Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.; Dementia Research Institute, London, UK.
Jazyk: angličtina
Zdroj: Translational psychiatry [Transl Psychiatry] 2024 Apr 22; Vol. 14 (1), pp. 194. Date of Electronic Publication: 2024 Apr 22.
DOI: 10.1038/s41398-024-02910-2
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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