We conducted portioning h2 enrichment analyses for PAU using LDSC in different models [13, 14]. First, we analyzed a baseline model consisting of 52 functional categories that included genomic features (coding, intron, UTR etc), regulatory annotations (promoter, enhancer etc), epigenomic annotations (H3K27ac, H3K4me1, H3K3me3 etc) and others (see ref [13] for details, Supplementary Figure 3). We then analyzed cell type group h2 enrichments with 10 cell types: central nervous system (CNS), adrenal and pancreas, immune and hematopoietic, skeletal muscle, gastrointestinal, liver, cardiovascular, connective tissue and bone, kidney, and other (see ref [13] for details, Supplementary Figure 2). Third, we used LDSC to test for enriched heritability in regions surrounding genes with the highest tissue-specific expression using 53 human tissue or cell type RNA-seq data from the Genotype-Tissue Expression Project (GTEx) [16], or enriched heritability in epigenetic markers from 396 human epigenetic annotations (six features in a subset of 88 primary cell types or tissues) from the Roadmap Epigenomics Consortium [15] (see ref [14] for details, Supplementary Figure 4, Supplementary Table 6). For each model, the number of tested annotations was used to calculate a Bonferroni corrected p-value < 0.05 as a significance threshold.
