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Table 1 Functional enrichment analysis of pleiotropy score

From: HOPS: a quantitative score reveals pervasive horizontal pleiotropy in human genetic variation is driven by extreme polygenicity of human traits and diseases

    \( {P}_m^{\mathrm{LD}} \) \( {P}_n^{\mathrm{LD}} \)
Variant effect predictor   UTR + 0.24 (± 0.01); P = 1.72 × 10− 234 + 0.69 (± 0.02); P = 2.16 × 10− 236
Coding synonymous + 0.24 (± 0.01); P = 2.49 × 10− 99 + 0.61 (± 0.03); P = 1.92 × 10− 76
Non-synonymous + 0.19 (± 0.01); P = 3.82 × 10− 82 + 0.48 (± 0.03); P = 3.62 × 10− 62
Roadmap Epigenomics   H327ac + 0.20 (± 0.01); P < 10− 308 + 0.54 (± 0.01); P < 10− 308
H3K27me3 + 0.02 (± 0.01); P = 1.40 × 10− 18 + 0.01 (± 0.01); P = 0.4
Active TSS + 0.20 (± 0.02); P = 1.42 × 10− 36 + 0.54 (± 0.04); P = 8.56 × 10− 34
Promoter Promoter Upstream TSS + 0.16 (± 0.01); P = 4.44 × 10− 130 + 0.43 (± 0.02); P = 4.33 × 10− 103
Promoter Downstream TSS 1 + 0.35 (± 0.01); P = 1.87 × 10− 220 + 0.92 (± 0.03); P = 3.59 × 10− 197
Promoter Downstream TSS 2 + 0.30 (± 0.01); P = 2.70 × 10− 203 + 0.86 (± 0.03); P = 3.44 × 10− 210
Transcription Transcribed - 5′ preferential + 0.29 (± 0.01); P < 10− 308 + 0.88 (± 0.01); P < 10− 308
Strong transcription + 0.38 (± 0.01); P < 10− 308 + 1.10 (± 0.01); P < 10− 308
Transcribed - 3′ preferential + 0.29 (± 0.01); P < 10− 308 + 0.82 (± 0.01); P < 10− 308
Weak transcription + 0.21 (± 0.01); P < 10− 308 + 0.60 (± 0.01); P < 10− 308
Transcription and regulation Transcribed and regulatory (Prom/Enh) + 0.36 (± 0.01); P < 10− 308 + 1.00 (± 0.02); P < 10− 308
Transcribed 5′ preferential and Enh + 0.35 (± 0.01); P < 10− 308 + 1.00 (± 0.01); P < 10− 308
Transcribed 3′ preferential and Enh + 0.33 (± 0.01); P < 10− 308 + 0.92 (± 0.02); P < 10− 308
Transcribed and Weak Enhancer + 0.32 (± 0.01); P < 10− 308 + 0.97 (± 0.01); P < 10− 308
Active enhancer Active Enhancer 1 + 0.13 (± 0.01); P = 4.54 × 10− 295 + 0.32 (± 0.01); P = 5.1 × 10− 216
Active Enhancer 2 + 0.11 (± 0.01); P = 2.64 × 10− 294 + 0.28 (± 0.01); P = 5.63 × 10− 238
Active Enhancer Flank + 0.11 (± 0.01); P < 10− 308 + 0.29 (± 0.01); P = 6.06 × 10− 270
Weak enhancer Weak Enhancer 1 + 0.07 (± 0.01); P = 2.79 × 10− 89 + 0.16 (± 0.01); P = 6.89 × 10− 60
Weak Enhancer 2 + 0.08 (± 0.01); P < 10− 308 + 0.23 (± 0.01); P = 6.52 × 10− 291
Primary H3K27ac possible Enhancer + 0.09 (± 0.01); P = 2.72 × 10− 259 + 0.24 (± 0.01); P = 1.53 × 10− 187
  Primary DNase + 0.03 (± 0.01); P = 3.83 × 10− 21 + 0.05 (± 0.01); P = 1.11 × 10− 7
ZNF genes & repeats + 0.08 (± 0.01); P = 1.29 × 10− 7 + 0.20 (± 0.04); P = 6.9 × 10− 7
Heterochromatin − 0. 20 (± 0.01); P < 10− 308 − 0.61 (± 0.01); P < 10− 308
Poised Promoter + 0.05 (± 0.01); P = 1.03 × 10− 35 + 0.09 (± 0.01); P = 2.27 × 10− 16
Bivalent Promoter + 0.17 (± 0.01); P = 1.28 × 10− 93 + 0.51 (± 0.03); P = 6.29 × 10− 88
Repressed Polycomb + 0.04 (± 0.01); P = 5.77 × 10− 42 + 0.06 (± 0.01); P = 1.48 × 10− 11
Quiescent/Low −0.41 (± 0.01); P < 10− 308 −1.20 (± 0.01); P < 10− 308
GTEx - number of genes the variant is an eQTL for   eGenes< 10 + 0.11 (± 0.01); P = 6.78 × 10− 186 + 0.28 (± 0.01); P = 1.04 × 10− 140
eGenes> 10 & < 15 + 0.19 (± 0.01); P = 4.72 × 10− 114 + 0.52 (± 0.02); P = 6.84 × 10− 99
eGenes> 15 & < 20 + 0.31 (± 0.02); P = 7.98 × 10− 52 + 0.88 (± 0.06); P = 5.38 × 10− 47
eGenes> 20 + 0.66 (± 0.06); P = 3.40 × 10− 27 + 2.07 (± 0.18); P = 1.35 × 10− 30
GTEx - number of tissues the variant is an eQTL for   eTissue< 30 + 0.10 (± 0.01); P = 1.84 × 10− 151 + 0.26 (± 0.01); P = 1.26 × 10− 114
eTissue> 30 & < 35 + 0.21 (± 0.01); P = 3.70 × 10− 187 + 0.54 (± 0.02); P = 6.80 × 10− 147
eTissue> 35 & < 40 + 0.36 (± 0.02); P = 1.11 × 10− 82 + 1.13 (± 0.06); P = 4.24 × 10− 92
eTissue> 40 + 0.35 (± 0.05); P = 2,42 × 10− 13 + 0.97 (± 0.14); P = 7.08 × 10− 12
International Mouse Phenotyping Consortium   Phenotypes > 1 + 0.06 (± 0.01); P = 1.91 × 10− 6 + 0.19 (± 0.04); P = 2.70 × 10− 7
Saccharomyces cerevisiae Morphological Database   Phenotypes > 1 + 0.09 (± 0.01); P = 4.48 × 10− 17 + 0.26 (± 0.03); P = 1.53 × 10− 18
  1. We grouped variants by (i) molecular function as annotated by Ensembl, (ii) predicted chromatin state as annotated by the NIH Roadmap Epigenomics Project, (iii) transcriptional effects as annotated by the NIH Genotype-Tissue Expression (GTex) Project, and (iv) effects on model organism phenotypes as annotated by the International Mouse Phenotyping Consortium (IMPC) and Saccharomyces Cerevisiae Morphological Database (SCMD). For each grouping, we computed the mean LD-corrected pleiotropy score and used two-sample Student’s t test to determine whether the mean was significantly different from the baseline. We found (i) that coding regions have higher pleiotropy scores than noncoding regions, (ii) that active promoters and enhancers have the highest pleiotropy scores and quiescent and heterochromatin have the lowest, (iii) that variants that control expression of more genes in more tissues have higher pleiotropy scores, and (iv) that genes associated with more than one model organism phenotype have higher pleiotropy scores