PMC:4157143 / 35010-36838 JSONTXT

{"project":"2_test","denotations":[{"id":"25192044-24092820-2055649","span":{"begin":1703,"end":1705},"obj":"24092820"}],"text":"One limitation of the study is that we did not observe many more large-effect eQTLs in the family than expected by chance; high FDRs were observed for all categories of large-effect eQTLs. This could suggest that there is not an overabundance of large-effect eQTLs specific to the family. It might also simply reflect limited power or imperfect comparison of effect sizes between cohorts, given that we explored by varying quantification pipelines, discovery-panel sizes, and methodologies for selecting testable variants. However, the enriched properties we identified for large-effect family eQTLs appear to be robust to such limitations, and we highlight that although there might not be a strong excess of large-effect eQTLs, the relative degree of effect between the family and population conveys meaningful properties of family eQTLs. For instance, as the degree of effect size increased in the family relative to the population, we observed an increasing enrichment of rare and potentially regulatory variants. Furthermore, such large-effect eQTLs in the family exhibited increasing enrichment in ASE, implicating a heterozygous causal variant. Additionally, the enrichment of family eQTLs among constrained and central genes was most extreme for the subset of genes in which a rare and potentially regulatory variant could be identified. These observations fit with population-genetic expectation given that rare variants can influence more essential genes because of a reduced impact of purifying selection. Furthermore, this is in contrast to the general properties of population eQTL genes; for increasing effect sizes, they have previously been shown to be less constrained and less central.19 Taken together, these results implicate an important role of rare regulatory variants in large-effect eQTLs in the family."}