Genetic pleiotropy between multiple sclerosis and schizophrenia but not bipolar disorder: differential involvement of immune-related gene loci

Andreassen, O. A., Harbo, H. F., Wang, Y., Thompson, W. K., Schork, A. J., Mattingsdal, M., Zuber, V., Bettella, F., Ripke, S., Kelsoe, J. R., Kendler, K. S., O'Donovan, M. C., Sklar, P., The Psychiatric Genomics Consortium (PGC), Mowry, Bryan, McEvoy, L. K., Desikan, R. S., Lie, B. A., Djurovic, S. and Dale, A. M. (2014) Genetic pleiotropy between multiple sclerosis and schizophrenia but not bipolar disorder: differential involvement of immune-related gene loci. Molecular Psychiatry, 20 2: 207-214. doi:10.1038/mp.2013.195


Author Andreassen, O. A.
Harbo, H. F.
Wang, Y.
Thompson, W. K.
Schork, A. J.
Mattingsdal, M.
Zuber, V.
Bettella, F.
Ripke, S.
Kelsoe, J. R.
Kendler, K. S.
O'Donovan, M. C.
Sklar, P.
The Psychiatric Genomics Consortium (PGC)
Mowry, Bryan
McEvoy, L. K.
Desikan, R. S.
Lie, B. A.
Djurovic, S.
Dale, A. M.
Title Genetic pleiotropy between multiple sclerosis and schizophrenia but not bipolar disorder: differential involvement of immune-related gene loci
Journal name Molecular Psychiatry   Check publisher's open access policy
ISSN 1359-4184
1476-5578
Publication date 2014-01-29
Sub-type Article (original research)
DOI 10.1038/mp.2013.195
Open Access Status Not yet assessed
Volume 20
Issue 2
Start page 207
End page 214
Total pages 8
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Abstract Converging evidence implicates immune abnormalities in schizophrenia (SCZ), and recent genome-wide association studies (GWAS) have identified immune-related single-nucleotide polymorphisms (SNPs) associated with SCZ. Using the conditional false discovery rate (FDR) approach, we evaluated pleiotropy in SNPs associated with SCZ (n=21 856) and multiple sclerosis (MS) (n=43 879), an inflammatory, demyelinating disease of the central nervous system. Because SCZ and bipolar disorder (BD) show substantial clinical and genetic overlap, we also investigated pleiotropy between BD (n=16 731) and MS. We found significant genetic overlap between SCZ and MS and identified 21 independent loci associated with SCZ, conditioned on association with MS. This enrichment was driven by the major histocompatibility complex (MHC). Importantly, we detected the involvement of the same human leukocyte antigen (HLA) alleles in both SCZ and MS, but with an opposite directionality of effect of associated HLA alleles (that is, MS risk alleles were associated with decreased SCZ risk). In contrast, we found no genetic overlap between BD and MS. Considered together, our findings demonstrate genetic pleiotropy between SCZ and MS and suggest that the MHC signals may differentiate SCZ from BD susceptibility
Keyword False discovery rate
HLA region
Multiple sclerosis
Polygenic pleiotropy
Q-Index Code CX
Q-Index Status Provisional Code
Institutional Status Non-UQ
Additional Notes Bryan Mowry is part of The Psychiatric Genomics Consortium

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
 
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