Tourette syndrome SNP-based heritability (h2g) from the GWAS meta-analysis was also used as a genome-wide probe to test whether aggregated Tourette syndrome genetic risk might be concentrated either in 52 specific functional genomic elements (e.g., promoters, enhancers, epigenetic marks) or in gene expression patterns from 10 grouped tissue/cell types using partitioned LDSC (22). Evolutionarily-conserved SNPs (2.6% of all SNPs) were enriched 16.5-fold for Tourette h2g, accounting for 42.3% of Tourette syndrome heritability (Pr(h2g)/Pr(SNPs)=16.5, SE=5.3, p=3.6×10−3, NS after correction). A parallel analysis including these evolutionarily-conserved SNPs plus 500-bp flanking windows (33% of all SNPs) was enriched 2.8-fold for Tourette h2g and accounted for 92.4% of Tourette syndrome heritability (Pr(hg2)/Pr(SNPs)=2.80, SE=0.46, p=1.0×10−4; p=0.005 after correction) (Figure S8). No other genomic annotations were significantly enriched for Tourette SNP-based heritability. In the cell-type analysis, significant enrichment was found only for CNS cell types, with 62.7% of Tourette syndrome heritability contributed by 14.8% of SNPs (p=4.2×10−8; p=4.2×10−7 after correction) (Figure S9).
