Publications

Detailed Information

Cross-disorder analysis of schizophrenia and 19 immune-mediated diseases identifies shared genetic risk

Cited 52 time in Web of Science Cited 59 time in Scopus
Authors

Pouget, Jennie G.; Han, Buhm; Wu, Yang; Mignot, Emmanuel; Ollila, Hanna M.; Barker, Jonathan; Spain, Sarah; Dand, Nick; Trembath, Richard; Martin, Javier; Mayes, Maureen D.; Bossini-Castillo, Lara; Lopez-Isac, Elena; Jin, Ying; Santorico, Stephanie A.; Spritz, Richard A.; Hakonarson, Hakon; Polychronakos, Constantin; Raychaudhuri, Soumya; Knight, Jo

Issue Date
2019-10
Publisher
Oxford University Press
Citation
Human Molecular Genetics, Vol.28 No.20, pp.3498-3513
Abstract
Many immune diseases occur at different rates among people with schizophrenia compared to the general population. Here, we evaluated whether this phenomenon might be explained by shared genetic risk factors. We used data from large genome-wide association studies to compare the genetic architecture of schizophrenia to 19 immune diseases. First, we evaluated the association with schizophrenia of 581 variants previously reported to be associated with immune diseases at genome-wide significance. We identified five variants with potentially pleiotropic effects. While colocalization analyses were inconclusive, functional characterization of these variants provided the strongest evidence for a model in which genetic variation at rs1734907 modulates risk of schizophrenia and Crohn's disease via altered methylation and expression of EPHB4-a gene whose protein product guides the migration of neuronal axons in the brain and the migration of lymphocytes towards infected cells in the immune system. Next, we investigated genome-wide sharing of common variants between schizophrenia and immune diseases using cross-trait LD score regression. Of the 11 immune diseases with available genome-wide summary statistics, we observed genetic correlation between six immune diseases and schizophrenia: inflammatory bowel disease (r(g) = 0.12 +/- 0.03, P = 2.49 x 10(-4)), Crohn's disease (r(g) = 0.097 +/- 0.06, P = 3.27 x 10(-3)), ulcerative colitis (r(g) = 0.11 +/- 0.04, P = 4.05 x 10(-3)), primary biliary cirrhosis (r(g) = 0.13 +/- 0.05, P = 3.98 x 10(-3)), psoriasis (r(g) = 0.18 +/- 0.07, P = 7.78 x 10(-3)) and systemic lupus erythematosus (r(g) = 0.13 +/- 0.05, P = 3.76 x 10(-3)). With the exception of ulcerative colitis, the degree and direction of these genetic correlations were consistent with the expected phenotypic correlation based on epidemiological data. Our findings suggest shared genetic risk factors contribute to the epidemiological association of certain immune diseases and schizophrenia.
ISSN
0964-6906
URI
https://hdl.handle.net/10371/191496
DOI
https://doi.org/10.1093/hmg/ddz145
Files in This Item:
There are no files associated with this item.
Appears in Collections:

Related Researcher

  • College of Medicine
  • Department of Medicine
Research Area Bioinformatics, Genomics, Statistical Genetics

Altmetrics

Item View & Download Count

  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Share