RT Journal Article SR Electronic T1 Polygenic analysis of schizophrenia and 19 immune diseases reveals modest pleiotropy JF bioRxiv FD Cold Spring Harbor Laboratory SP 068684 DO 10.1101/068684 A1 Jennie G Pouget A1 Schizophrenia Working Group of the Psychiatric Genomics Consortium A1 Buhm Han A1 Emmanuel Mignot A1 Hanna M Ollila A1 Jonathan Barker A1 Sarah Spain A1 Nick Dand A1 Richard Trembath A1 Javier Martin A1 Maureen D Mayes A1 Lara Bossini-Castillo A1 Elena López-Isac A1 Ying Jin A1 Stephanie A Santorico A1 Richard A Spritz A1 Soumya Raychaudhuri A1 Jo Knight YR 2016 UL http://biorxiv.org/content/early/2016/08/09/068684.abstract AB Epidemiological studies have revealed that schizophrenia and autoimmune diseases co-occur in the general population at higher than expected rates. Here, we evaluated whether the epidemiologic correlation between immune diseases and schizophrenia might be explained by shared genetic risk factors. We first evaluated the association of 581 variants previously reported to be associated with 19 different immune diseases at genome-wide significance in a recent genome-wide association study (GWAS) of schizophrenia (N=35,476 cases and 46,839 controls). We identified nine variants with pleiotropic effects, associated with both schizophrenia and autoimmunity. Five of these pleiotropic variants were located outside of the HLA region, and mapped to genes with known roles in calcium signaling. We then evaluated whether polygenic risk scores for immune diseases, which take into account the collective effects of all SNPs (p<1 in association with the immune disease of interest), predicted schizophrenia. Among 14 immune diseases with available genome-wide summary statistics, higher polygenic risk scores for narcolepsy (liability-scale R2=0.02%, p=4.1x10−4), primary biliary cirrhosis (R2=0.04%, p=1.4x10−8), psoriasis (R2=0.02%, p=3.6x10−5), systemic lupus erythematosus (R2=0.04%, p=2.2x10−8), type 1 diabetes (R2=0.03%, p=2.0x10−6), and ulcerative colitis (R2=0.02%, p=4.3x10−4) were significantly associated with schizophrenia. We also observed suggestive evidence of sex-dependent pleiotropy between schizophrenia and multiple sclerosis (interaction p=0.02), with genetic risk scores for multiple sclerosis associated with greater risk of schizophrenia among males but not females. Our findings reveal the presence of modest pleiotropy between schizophrenia and several autoimmune diseases, which in some cases may be sex-dependent.