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

Lee, S. Hong, Byrne, Enda M., Hultman, Christina M., Kahler, Anna, Vinkhuyzen, Anna A. E., Ripke, Stephan, Andreassen, Ole A., Frisell, Thomas, Gusev, Alexander, Hu, Xinli, Karlsson, Robert, Mantzioris, Vasilis X., McGrath, John J., Mehta, Divya, Stahl, Eli A., Zhao, Qiongyi, Kendler, Kenneth S., Sullivan, Patrick F., Price, Alkes L., O'Donovan, Michael, Okada, Yukinori, Mowry, Bryan J., Raychaudhuri, Soumya, Wray, Naomi R., Schizophrenia Working Group of the Psychiatric Genomics Consortium, Rheumatoid Arthritis Consortium International and Visscher, Peter M . (2015) New data and an old puzzle: the negative association between schizophrenia and rheumatoid arthritis. International Journal of Epidemiology, 44 5: 1-16. doi:10.1093/ije/dyv136

Author Lee, S. Hong
Byrne, Enda M.
Hultman, Christina M.
Kahler, Anna
Vinkhuyzen, Anna A. E.
Ripke, Stephan
Andreassen, Ole A.
Frisell, Thomas
Gusev, Alexander
Hu, Xinli
Karlsson, Robert
Mantzioris, Vasilis X.
McGrath, John J.
Mehta, Divya
Stahl, Eli A.
Zhao, Qiongyi
Kendler, Kenneth S.
Sullivan, Patrick F.
Price, Alkes L.
O'Donovan, Michael
Okada, Yukinori
Mowry, Bryan J.
Raychaudhuri, Soumya
Wray, Naomi R.
Schizophrenia Working Group of the Psychiatric Genomics Consortium
Rheumatoid Arthritis Consortium International
Visscher, Peter M .
Title New data and an old puzzle: the negative association between schizophrenia and rheumatoid arthritis
Journal name International Journal of Epidemiology   Check publisher's open access policy
ISSN 0300-5771
Publication date 2015-01-01
Sub-type Article (original research)
DOI 10.1093/ije/dyv136
Open Access Status Not Open Access
Volume 44
Issue 5
Start page 1
End page 16
Total pages 16
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Language eng
Formatted 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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2016 Collection
School of Medicine Publications
UQ Diamantina Institute Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 11 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 13 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Wed, 09 Dec 2015, 19:37:29 EST by Susan Day on behalf of Queensland Brain Institute