Previous studies of model organisms using gene knock-out experiments suggested that pleiotropic risk loci may undergo stronger selection than non-pleiotropic loci (Hill and Zhang, 2012). However, we found no evidence that pleiotropic risk variants are under stronger evolutionary constraints (Table S6.4). Various comparative genomics resources, including PhyloP (Pollard et al., 2010), PhastCons (Siepel et al., 2005), and GERP++ (Davydov et al., 2010), showed our top loci to have similar properties regardless of the extent of pleiotropy. Neither did we find differences between disorder-specific lead SNPs and pleiotropic SNPs with respect to their minor allele frequencies, average heterozygosity, or predicted allele ages (Kiezun et al., 2013). Pleiotropic and non-pleiotropic SNPs also did not differ in terms of the distance to nearest genes, distance to splicing sites, chromosome compositions, and predicted functional consequences of non-coding regulatory elements.
