As a negative control analysis, we conducted bivariate analyses between each of the PGC data sets and Crohn’s disease samples from the International IBD Genetics Consortium (IIBDGC)42. Although onset of major depressive disorder is not uncommon after diagnosis with Crohn’s disease43 and although gastrointestinal pathology is a common comorbidity with ASD44, there is no strong evidence of a familial relationship between psychiatric disorders and Crohn’s disease. Despite substantial hSNP 2 values for Crohn’s disease (0.19, 0.01 s.e.), none of the SNP-based coheritabilities with the psychiatric disorders differed significantly from zero (Fig. 3c, Supplementary Table 6 and Supplementary Note). Lastly, genomic partitioning by annotation of the variance in Crohn’s disease explained by SNPs showed, as expected, no excess of variance attributable to SNPs in the CNS+ gene set (Fig. 2). Our results provide no evidence of common genetic pleiotropy in Crohn’s disease and ASD, consistent with a non-genetic, for example, microbial45, explanation for the comorbidity of gastrointestinal symptoms in ASD.
