| Literature DB >> 31211845 |
Jennie G Pouget1,2,3, Buhm Han4, Yang Wu5, Emmanuel Mignot6, Hanna M Ollila6,7,8, Jonathan Barker9,10, Sarah Spain9,11, Nick Dand9, Richard Trembath9,12, Javier Martin13, Maureen D Mayes14, Lara Bossini-Castillo11, Elena López-Isac13, Ying Jin15,16, Stephanie A Santorico15,17,18, Richard A Spritz15,16, Hakon Hakonarson19, Constantin Polychronakos20, Soumya Raychaudhuri21,22,23,24,25,26, Jo Knight27.
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 (rg = 0.12 ± 0.03, P = 2.49 × 10-4), Crohn's disease (rg = 0.097 ± 0.06, P = 3.27 × 10-3), ulcerative colitis (rg = 0.11 ± 0.04, P = 4.05 × 10-3), primary biliary cirrhosis (rg = 0.13 ± 0.05, P = 3.98 × 10-3), psoriasis (rg = 0.18 ± 0.07, P = 7.78 × 10-3) and systemic lupus erythematosus (rg = 0.13 ± 0.05, P = 3.76 × 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.Entities:
Mesh：
Year: 2019 PMID： 31211845 PMCID： PMC6891073 DOI： 10.1093/hmg/ddz145
Source DB: PubMed Journal: Hum Mol Genet ISSN： 0964-6906 Impact factor: 6.150