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  The role of the major histocompatibility complex region in cognition and brain structure: A schizophrenia GWAS follow-up

Walters, J., Rujescu, D., Franke, B., Giegling, I., Vasquez, A., Hargreaves, A., et al. (2013). The role of the major histocompatibility complex region in cognition and brain structure: A schizophrenia GWAS follow-up. American Journal of Psychiatry, 170, 877-885. doi:10.1176/appi.ajp.2013.12020226.

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Hoogman_2013_JourAmePsy.pdf (Publisher version), 535KB
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 Creators:
Walters, J.T.R., Author
Rujescu, D., Author
Franke, B., Author
Giegling, I., Author
Vasquez, A.A., Author
Hargreaves, A., Author
Russo, G., Author
Morris, D.W., Author
Hoogman, Martine1, 2, Author           
Da Costa, A., Author
Moskvina, V., Author
Fernandez, G., Author
Gill, M., Author
Corvin, A., Author
O'Donovan, M.C., Author
Donohoe, G., Author
Owen, M.J., Author
Affiliations:
1Donders Institute for Brain, Cognition and Behaviour, ou_persistent22              
2Language and Genetics Department, MPI for Psycholinguistics, Max Planck Society, ou_792549              

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 Abstract: Objective The authors investigated the effects of recently identified genome-wide significant schizophrenia genetic risk variants on cognition and brain structure. Method A panel of six single-nucleotide polymorphisms (SNPs) was selected to represent genome-wide significant loci from three recent genome-wide association studies (GWAS) for schizophrenia and was tested for association with cognitive measures in 346 patients with schizophrenia and 2,342 healthy comparison subjects. Nominally significant results were evaluated for replication in an independent case-control sample. For SNPs showing evidence of association with cognition, associations with brain structural volumes were investigated in a large independent healthy comparison sample. Results Five of the six SNPs showed no significant association with any cognitive measure. One marker in the major histocompatibility complex (MHC) region, rs6904071, showed independent, replicated evidence of association with delayed episodic memory and was significant when both samples were combined. In the combined sample of up to 3,100 individuals, this SNP was associated with widespread effects across cognitive domains, although these additional associations were no longer significant after adjusting for delayed episodic memory. In the large independent structural imaging sample, the same SNP was also associated with decreased hippocampal volume. Conclusions The authors identified a SNP in the MHC region that was associated with cognitive performance in patients with schizophrenia and healthy comparison subjects. This SNP, rs6904071, showed a replicated association with episodic memory and hippocampal volume. These findings implicate the MHC region in hippocampal structure and functioning, consistent with the role of MHC proteins in synaptic development and function. Follow-up of these results has the potential to provide insights into the pathophysiology of schizophrenia and cognition.

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Language(s): eng - English
 Dates: 2013
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1176/appi.ajp.2013.12020226
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Title: American Journal of Psychiatry
  Other : Am. J. Psychiat.
Source Genre: Journal
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Publ. Info: Baltimore : American Psychiatric Association
Pages: - Volume / Issue: 170 Sequence Number: - Start / End Page: 877 - 885 Identifier: ISSN: 0002-953X
CoNE: https://pure.mpg.de/cone/journals/resource/110985822459324