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The role of critical immune genes in brain disorders: insights from neuroimaging immunogenetics

Genetic variants in the human leukocyte antigen and killer cell immunoglobulin-like receptor regions have been associated with many brain-related diseases, but how they shape brain structure and function remains unclear. To identify the genetic variants in HLA and KIR genes associated with human bra...

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Autores principales: Bian, Beilei, Couvy-Duchesne, Baptiste, Wray, Naomi R., McRae, Allan F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9014537/
https://www.ncbi.nlm.nih.gov/pubmed/35441133
http://dx.doi.org/10.1093/braincomms/fcac078
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author Bian, Beilei
Couvy-Duchesne, Baptiste
Wray, Naomi R.
McRae, Allan F.
author_facet Bian, Beilei
Couvy-Duchesne, Baptiste
Wray, Naomi R.
McRae, Allan F.
author_sort Bian, Beilei
collection PubMed
description Genetic variants in the human leukocyte antigen and killer cell immunoglobulin-like receptor regions have been associated with many brain-related diseases, but how they shape brain structure and function remains unclear. To identify the genetic variants in HLA and KIR genes associated with human brain phenotypes, we performed a genetic association study of ∼30 000 European unrelated individuals using brain MRI phenotypes generated by the UK Biobank (UKB). We identified 15 HLA alleles in HLA class I and class II genes significantly associated with at least one brain MRI-based phenotypes (P < 5 × 10(−8)). These associations converged on several main haplotypes within the HLA. In particular, the human leukocyte antigen alleles within an ancestral haplotype 8.1 were associated with multiple MRI measures, including grey matter volume, cortical thickness (TH) and diffusion MRI (dMRI) metrics. These alleles have been strongly associated with schizophrenia. Additionally, associations were identified between HLA-DRB1*04∼DQA1*03:01∼DQB1*03:02 and isotropic volume fraction of diffusion MRI in multiple white matter tracts. This haplotype has been reported to be associated with Parkinson’s disease. These findings suggest shared genetic associations between brain MRI biomarkers and brain-related diseases. Additionally, we identified 169 associations between the complement component 4 (C4) gene and imaging phenotypes. We found that C4 gene copy number was associated with cortical TH and dMRI metrics. No KIR gene copy numbers were associated with image-derived phenotypes at genome-wide threshold. To address the multiple testing burden in the phenome-wide association study, we performed a multi-trait association analysis using trait-based association test that uses extended Simes procedure and identified MRI image-specific associations. This study contributes to insight into how critical immune genes affect brain-related traits as well as the development of neurological and neuropsychiatric disorders.
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spelling pubmed-90145372022-04-18 The role of critical immune genes in brain disorders: insights from neuroimaging immunogenetics Bian, Beilei Couvy-Duchesne, Baptiste Wray, Naomi R. McRae, Allan F. Brain Commun Original Article Genetic variants in the human leukocyte antigen and killer cell immunoglobulin-like receptor regions have been associated with many brain-related diseases, but how they shape brain structure and function remains unclear. To identify the genetic variants in HLA and KIR genes associated with human brain phenotypes, we performed a genetic association study of ∼30 000 European unrelated individuals using brain MRI phenotypes generated by the UK Biobank (UKB). We identified 15 HLA alleles in HLA class I and class II genes significantly associated with at least one brain MRI-based phenotypes (P < 5 × 10(−8)). These associations converged on several main haplotypes within the HLA. In particular, the human leukocyte antigen alleles within an ancestral haplotype 8.1 were associated with multiple MRI measures, including grey matter volume, cortical thickness (TH) and diffusion MRI (dMRI) metrics. These alleles have been strongly associated with schizophrenia. Additionally, associations were identified between HLA-DRB1*04∼DQA1*03:01∼DQB1*03:02 and isotropic volume fraction of diffusion MRI in multiple white matter tracts. This haplotype has been reported to be associated with Parkinson’s disease. These findings suggest shared genetic associations between brain MRI biomarkers and brain-related diseases. Additionally, we identified 169 associations between the complement component 4 (C4) gene and imaging phenotypes. We found that C4 gene copy number was associated with cortical TH and dMRI metrics. No KIR gene copy numbers were associated with image-derived phenotypes at genome-wide threshold. To address the multiple testing burden in the phenome-wide association study, we performed a multi-trait association analysis using trait-based association test that uses extended Simes procedure and identified MRI image-specific associations. This study contributes to insight into how critical immune genes affect brain-related traits as well as the development of neurological and neuropsychiatric disorders. Oxford University Press 2022-03-31 /pmc/articles/PMC9014537/ /pubmed/35441133 http://dx.doi.org/10.1093/braincomms/fcac078 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Bian, Beilei
Couvy-Duchesne, Baptiste
Wray, Naomi R.
McRae, Allan F.
The role of critical immune genes in brain disorders: insights from neuroimaging immunogenetics
title The role of critical immune genes in brain disorders: insights from neuroimaging immunogenetics
title_full The role of critical immune genes in brain disorders: insights from neuroimaging immunogenetics
title_fullStr The role of critical immune genes in brain disorders: insights from neuroimaging immunogenetics
title_full_unstemmed The role of critical immune genes in brain disorders: insights from neuroimaging immunogenetics
title_short The role of critical immune genes in brain disorders: insights from neuroimaging immunogenetics
title_sort role of critical immune genes in brain disorders: insights from neuroimaging immunogenetics
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9014537/
https://www.ncbi.nlm.nih.gov/pubmed/35441133
http://dx.doi.org/10.1093/braincomms/fcac078
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