We next compared h2 for all genes to multiple external “predictors”1,36–44 using an enrichment statistic rigorously evaluated under permutations of twin zygosity (Table 2). Heritability was strongly associated with expression mean and variance. Regional GC content was negatively associated with h2 after mean expression correction. This negative association was surprising, as GC content ± 5kb from the TSS was positively correlated with gene density (r=0.40) and each modestly with mean expression (r=0.11 and r=0.10). Accordingly, after correcting for mean expression, the negative association with gene density was even stronger (Table 2, Figure 2a). Genes with recent evolutionary acceleration in primates and humans42 showed significant positive association with h2 after mean correction (Figure 2b and Table 2). HomoloGene conservation was highly significant, although attenuated after correction. Associations between h2 and numerous KEGG and GO pathways were also highly significant (Supplementary Table 3). Interestingly, all pathway associations with h2 were positive, except two related to sensory perception and smell (GO:0050907 and GO:0050911).
