Authors:
S. Hong Lee, S. Hong Lee, Enda M. Byrne, Christina M. Hultman, Anna K. Kähler, Anna A. E. Vinkhuyzen, Stephan Ripke, Stephan Ripke, Stephan Ripke, Ole A. Andreassen, Ole A. Andreassen, Thomas Frisell, Alexander Gusev, Alexander Gusev, Xinli Hu, Robe (...)
S. Hong Lee, S. Hong Lee, Enda M. Byrne, Christina M. Hultman, Anna K. Kähler, Anna A. E. Vinkhuyzen, Stephan Ripke, Stephan Ripke, Stephan Ripke, Ole A. Andreassen, Ole A. Andreassen, Thomas Frisell, Alexander Gusev, Alexander Gusev, Xinli Hu, Robert Karlsson, Vasilis X Mantzioris, John J. McGrath, John J. McGrath, Divya Mehta, Eli A. Stahl, Qiongyi Zhao, Kenneth S. Kendler, Patrick F. Sullivan, Alkes L. Price, Alkes L. Price, Michael Conlon O'Donovan, Michael Conlon O'Donovan, Yukinori Okada, Bryan J. Mowry, Bryan J. Mowry, Soumya Raychaudhuri, Naomi R. Wray, William Byerley, Wiepke Cahn, Rita M. Cantor, Sven Cichon, Sven Cichon, Sven Cichon, Paul Cormican, David Curtis, Srdjan Djurovic, Valentina Escott-Price, Pablo V. Gejman, Lyudmila Georgieva, Ina Giegling, Thomas Hansen, Thomas Hansen, Andres Ingason, Andres Ingason, Yunjung Kim, Bettina Konte, Phil Lee, Andrew M. McIntosh, Andrew M. McIntosh, Andrew McQuillin, Derek W. Morris, Markus M. Nöthen, Colm O'Dushlaine, Ann Olincy, Line Olsen, Line Olsen, Carlos N. Pato, Michele T. Pato, Benjamin S. Pickard, Benjamin S. Pickard, Danielle Posthuma, Henrik B. Rasmussen, Henrik B. Rasmussen, Marcella Rietschel, Dan Rujescu, Thomas G. Schulze, Thomas G. Schulze, Jeremy M. Silverman, Srinivasa Thirumalai, Thomas Werge, Thomas Werge, Thomas Werge, Ingrid Agartz, Farooq Amin, Maria Helena Pinto de Azevedo, Nicholas Bass, Donald W. Black, Douglas Blackwood, Richard Bruggeman, Nancy G. Buccola, Khalid Choudhury, Robert C. Cloninger, Aiden Corvin, Nicholas John Craddock, Mark J. Daly, Mark J. Daly, Susmita Datta, Gary Donohoe, Jubao Duan, Frank Dudbridge, Ayman H. Fanous, Ayman H. Fanous, Robert Freedman, Nelson B. Freimer, Marion Friedl, Michael Gill, Hugh Gurling, Lieuwe de Haan, Marian L. Hamshere, Annette M. Hartmann, Peter Holmans, René S. Kahn, Matthew C. Keller, Elaine Kenny, George Kirov, Lydia Krabbendam, Robert Krasucki, Jacob Lawrence, Todd Lencz, Todd Lencz, Douglas F. Levinson, Jeffrey A. Lieberman, Danyu Lin, Don H. Linszen, Patrik K. E. Magnusson, Wolfgang Maier, Anil K. Malhotra, Anil K. Malhotra, Manuel Mattheisen, Morten Mattingsdal, Steven A. McCarroll, Helena Medeiros, Ingrid Melle, Ingrid Melle, Vihra Milanova, Inez Myin-Germeys, Benjamin M. Neale, Benjamin M. Neale, Roel A. Ophoff, Roel A. Ophoff, Michael John Owen, Jonathan Pimm, Shaun Purcell, Shaun Purcell, Shaun Purcell, Vinay Puri, Digby Quested, Lizzy Rossin, Douglas M. Ruderfer, Alan R. Sanders, Jianxin Shi, Pamela Sklar, David St Clair, T. Scott Stroup, Jim van Os, Peter M. Visscher, Peter M. Visscher, Durk Wiersma, Stanley Zammit, S. Louis Bridges, Hyon K. Choi, Hyon K. Choi, Marieke J H Coenen, Niek de Vries, Philippe Dieud, Jeff Greenberg, Tom W J Huizinga, Leonid Padyukov, Katherine A. Siminovitch, Katherine A. Siminovitch, Paul P. Tak, Paul P. Tak, Paul P. Tak, Jane Worthington, Jane Worthington, Philip L. De Jager, Philip L. De Jager, Joshua C. Denny, Peter K. Gregersen, Lars Klareskog, Xavier Mariette, Robert M. Plenge, Robert M. Plenge, Mart A F J van de Laar, Piet L. C. M. van Riel
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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-wid (...)
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. Refereed/Peer-reviewed
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