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New data and an old puzzle: the negative association between schizophrenia and rheumatoid arthritis

Lee, S. Hong and Byrne, Enda M. and Hultman, Christina M. and Kähler, Anna and Vinkhuyzen, Anna AE and Ripke, Stephan and Andreassen, Ole A. and Frisell, Thomas and Gusev, Alexander and Hu, Xinli and Karlsson, Robert and Mantzioris, Vasilis X. and McGrath, John J. and Mehta, Divya and Stahl, Eli A. and Zhao, Qiongyi and Kendler, Kenneth S. and Sullivan, Patrick F. and Price, Alkes L. and O'Donovan, Michael and Okada, Yukinori and Mowry, Bryan J. and Raychaudhuri, Soumya and Wray, Naomi R. and Schizophrenia Working Group of the Psychiatric Genomics, Consortium and Rheumatoid Arthritis Consortium, International. (2015) New data and an old puzzle: the negative association between schizophrenia and rheumatoid arthritis. International Journal of Epidemiology, 44 (5). pp. 1706-1721.

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Official URL: https://edoc.unibas.ch/61564/

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Abstract

BACKGROUND: A long-standing epidemiological puzzle is the reduced rate of rheumatoid arthritis (RA) in those with schizophrenia (SZ) and vice versa. Traditional epidemiological approaches to determine if this negative association is underpinned by genetic factors would test for reduced rates of one disorder in relatives of the other, but sufficiently powered data sets are difficult to achieve. The genomics era presents an alternative paradigm for investigating the genetic relationship between two uncommon disorders.
METHODS: We use genome-wide common single nucleotide polymorphism (SNP) data from independently collected SZ and RA case-control cohorts to estimate the SNP correlation between the disorders. We test a genotype X environment (GxE) hypothesis for SZ with environment defined as winter- vs summer-born.
RESULTS: We estimate a small but significant negative SNP-genetic correlation between SZ and RA (-0.046, s.e. 0.026, P = 0.036). The negative correlation was stronger for the SNP set attributed to coding or regulatory regions (-0.174, s.e. 0.071, P = 0.0075). Our analyses led us to hypothesize a gene-environment interaction for SZ in the form of immune challenge. We used month of birth as a proxy for environmental immune challenge and estimated the genetic correlation between winter-born and non-winter born SZ to be significantly less than 1 for coding/regulatory region SNPs (0.56, s.e. 0.14, P = 0.00090).
CONCLUSIONS: Our results are consistent with epidemiological observations of a negative relationship between SZ and RA reflecting, at least in part, genetic factors. Results of the month of birth analysis are consistent with pleiotropic effects of genetic variants dependent on environmental context.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Human Genetics (Cichon)
UniBasel Contributors:Cichon, Sven
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Oxford University Press
ISSN:0300-5771
e-ISSN:1464-3685
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:14 Sep 2018 15:32
Deposited On:14 Sep 2018 15:32

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