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

Lee, S. H. and Byrne, E. M. and Hultman, C. M. and Kahler, A. and Vinkhuyzen, A. A. and Ripke, S. and Andreassen, O. A. and Frisell, T. and Gusev, A. and Hu, X. and Karlsson, R. and Mantzioris, V. X. and McGrath, J. J. and Mehta, D. and Stahl, E. A. and Zhao, Q. and Kendler, K. S. and Sullivan, P. F. and Price, A. L. and O'Donovan, M. and Okada, Y. and Mowry, B. J. and Raychaudhuri, S. and Wray, N. R. and Schizophrenia Working Group of the Psychiatric Genomics, Consortium and Rheumatoid Arthritis Consortium, International and Schizophrenia Working Group of the Psychiatric Genomics Consorti, Authors and Byerley, W. and Cahn, W. and Cantor, R. M. and Cichon, S. and Cormican, P. and Curtis, D. and Djurovic, S. and Escott-Price, V. and Gejman, P. V. and Georgieva, L. and Giegling, I. and Hansen, T. F. and Ingason, A. and Kim, Y. and Konte, B. and Lee, P. H. and McIntosh, A. and McQuillin, A. and Morris, D. W. and Nothen, M. M. and O'Dushlaine, C. and Olincy, A. and Olsen, L. and Pato, C. N. and Pato, M. T. and Pickard, B. S. and Posthuma, D. and Rasmussen, H. B. and Rietschel, M. and Rujescu, D. and Schulze, T. G. and Silverman, J. M. and Thirumalai, S. and Werge, T. and Agartz, I. and Amin, F. and Azevedo, M. H. and Bass, N. and Black, D. W. and Blackwood, D. H. and Bruggeman, R. and Buccola, N. G. and Choudhury, K. and Cloninger, R. C. and Corvin, A. and Craddock, N. and Daly, M. J. and Datta, S. and Donohoe, G. J. and Duan, J. and Dudbridge, F. and Fanous, A. and Freedman, R. and Freimer, N. B. and Friedl, M. and Gill, M. and Gurling, H. and De Haan, L. and Hamshere, M. L. and Hartmann, A. M. and Holmans, P. A. and Kahn, R. S. and Keller, M. C. and Kenny, E. and Kirov, G. K. and Krabbendam, L. and Krasucki, R. and Lawrence, J. and Lencz, T. and Levinson, D. F. and Lieberman, J. A. and Lin, D. Y. and Linszen, D. H. and Magnusson, P. K. and Maier, W. and Malhotra, A. K. and Mattheisen, M. and Mattingsdal, M. and McCarroll, S. A. and Medeiros, H. and Melle, I. and Milanova, V. and Myin-Germeys, I. and Neale, B. M. and Ophoff, R. A. and Owen, M. J. and Pimm, J. and Purcell, S. M. and Puri, V. and Quested, D. J. and Rossin, L. and Ruderfer, D. and Sanders, A. R. and Shi, J. and Sklar, P. and St Clair, D. and Stroup, T. S. and Van Os, J. and Visscher, P. M. and Wiersma, D. and Zammit, S. and Rheumatoid Arthritis Consortium International, Authors and Bridges, S. L. and Jr., and Choi, H. K. and Coenen, M. J. and de Vries, N. and Dieud, P. and Greenberg, J. D. and Huizinga, T. W. and Padyukov, L. and Siminovitch, K. A. and Tak, P. P. and Worthington, J. and De Jager, P. L. and Denny, J. C. and Gregersen, P. K. and Klareskog, L. and Mariette, X. and Plenge, R. M. and van Laar, M. and van Riel, P.. (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/61727/

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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 > Applied Microbiology Research (Egli)
UniBasel Contributors:Egli, Adrian and Cichon, Sven
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Oxford University Press
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:26 Oct 2023 15:40
Deposited On:20 Oct 2018 12:32

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