PMC:4157143 / 41226-42995 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/4157143","sourcedb":"PMC","sourceid":"4157143","source_url":"https://www.ncbi.nlm.nih.gov/pmc/4157143","text":"Enrichment of Rare Variants in Large-Effect eQTLs\n(A) Enrichment of rare and potentially regulatory variants near the TSS of large-effect (β) cis-eQTL genes. Variants are restricted to those with a MAF \u003c 0.01, within ENCODE TF binding and DNase I hypersensitivity peaks, and with a PhyloP score \u003e 1. We observed increased enrichment of rare regulatory variants near the TSS of larger-effect-size genes in the family.\n(B) Enrichment of potentially regulatory variants depends on allele frequency and relative effect sizes. We ranked genes (x axis) on the basis of how often their effect sizes in the family were greater than their effect sizes in the population subsamples, which is also 1 − their empirical p values (see Material and Methods). Variants are restricted to those within \u003c100 kb of the TSS, within ENCODE TF binding and DNase I hypersensitivity peaks, and with a PhyloP score \u003e 1. We observed that variant enrichment was dependent on whether the variant was rare (blue) or not (gray). We calculated enrichment by dividing the proportion of genes with such an annotated rare variant in each effect-size bin by the proportion of genes with an annotated rare variant across all effect-size bins.\n(C) Conservation scores and allele frequency predict genes with a larger effect in the family than in the population. We restricted to variants within \u003c100 kb of the TSS, within ENCODE TF binding and DNase I hypersensitivity peaks, and with different PhyloP thresholds. Proportions were computed by π1 statistics on permutation-based p values of family effect larger than population effect. We observed that rare and highly conserved variants overlapping epigenomic data (light blue) were highly predictive of a larger effect in the family than in the population.","divisions":[{"label":"p","span":{"begin":0,"end":49}},{"label":"p","span":{"begin":50,"end":416}},{"label":"p","span":{"begin":417,"end":1205}}],"tracks":[]}