English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

A schizophrenia-associated HLA locus affects thalamus volume and asymmetry

MPS-Authors
/persons/resource/persons27681

Brucato,  Nicolas
Language and Genetics Department, MPI for Psycholinguistics, Max Planck Society;
Leiden University Centre for Linguistics;

/persons/resource/persons22322

Guadalupe,  Tulio
Language and Genetics Department, MPI for Psycholinguistics, Max Planck Society;
International Max Planck Research School for Language Sciences, MPI for Psycholinguistics, Max Planck Society, Nijmegen, NL;

/persons/resource/persons4427

Fisher,  Simon E.
Language and Genetics Department, MPI for Psycholinguistics, Max Planck Society;
Donders Institute for Brain, Cognition and Behaviour, External Organizations;

/persons/resource/persons4382

Francks,  Clyde
Language and Genetics Department, MPI for Psycholinguistics, Max Planck Society;

Fulltext (public)

Brucato_Etal_BBI_2015.pdf
(Publisher version), 775KB

Supplementary Material (public)
There is no public supplementary material available
Citation

Brucato, N., Guadalupe, T., Franke, B., Fisher, S. E., & Francks, C. (2015). A schizophrenia-associated HLA locus affects thalamus volume and asymmetry. Brain, Behavior, and Immunity, 46, 311-318. doi:10.1016/j.bbi.2015.02.021.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0024-E5E6-3
Abstract
Genes of the Major Histocompatibility Complex (MHC) have recently been shown to have neuronal functions in the thalamus and hippocampus. Common genetic variants in the Human Leukocyte Antigens (HLA) region, human homologue of the MHC locus, are associated with small effects on susceptibility to schizophrenia, while volumetric changes of the thalamus and hippocampus have also been linked to schizophrenia. We therefore investigated whether common variants of the HLA would affect volumetric variation of the thalamus and hippocampus. We analyzed thalamus and hippocampus volumes, as measured using structural magnetic resonance imaging, in 1.265 healthy participants. These participants had also been genotyped using genome-wide single nucleotide polymorphism (SNP) arrays. We imputed genotypes for single nucleotide polymorphisms at high density across the HLA locus, as well as HLA allotypes and HLA amino acids, by use of a reference population dataset that was specifically targeted to the HLA region. We detected a significant association of the SNP rs17194174 with thalamus volume (nominal P=0.0000017, corrected P=0.0039), as well as additional SNPs within the same region of linkage disequilibrium. This effect was largely lateralized to the left thalamus and is localized within a genomic region previously associated with schizophrenia. The associated SNPs are also clustered within a potential regulatory element, and a region of linkage disequilibrium that spans genes expressed in the thalamus, including HLA-A. Our data indicate that genetic variation within the HLA region influences the volume and asymmetry of the human thalamus. The molecular mechanisms underlying this association may relate to HLA influences on susceptibility to schizophrenia