Several methods have now been used to examine quantitative SNP-based genetic relationships between psychiatric and immune-related phenotypes, including restricted maximum likelihood (REML) co-heritability, polygenic risk scores, genetic analysis incorporating pleiotropy and annotations, and other permutation-based methods (Cross-Disorder Group of the Psychiatric Genomics Consortium 2013; Lee et al. 2013; Pouget et al. 2016; Wang et al. 2015). Different approaches rest on unique assumptions, test different sets of hypotheses, and appear prone to generating sometimes conflicting results. Using several approaches that were not dependent on the directionality of a given SNP’s effect, Wang and colleagues concluded that many (24 of 35) pairs of psychiatric and immune-related phenotypes shared a statistically significant proportion of risk-associated loci; among these findings was a significant genetic overlap between BD (as well as SZ) and UC (Wang et al. 2015). However, many of the other relationships identified in that study were not significant in the present study. Another recent study demonstrated that polygenic risk scores reflecting additive risk for several autoimmune diseases can explain a small proportion of variance in SZ case-control status, yet the genome-wide significant
