<p>In order to evaluate whether rare regulatory variants in the vicinity of promoters are likely to impact gene expression, we conducted a novel burden test for rare variants at the extreme of expression. After targeted sequencing of 2kb promoter regions of 472 genes in 410 healthy adults, burden tests were performed by calculating the summed rare allele counts in ranked expression level bins using Illumina whole blood microarray gene expression data. The results clearly show an enrichment of rare variants at both extremes of gene expression. The rare regulatory variant effects were also partitioned into subsets of genes based on their regulatory functions, positions relative to transcription start sites, disease relatedness, with some intriguing biases. The enrichment of rare regulatory variants in extremely expressed genes was replicated in an independent sample of 75 individuals with RNASeq and whole genome sequence information. Participants were from the Emory-Georgia Tech Center for Health Discovery and Well Being (CHDWB) longitudinal cohort study, but only baseline gene expression data was used.</p>

Center for Health Discovery and Well Being (CHDWB)

Fitness Centers study with OTHER data on dbGaP (410 participants)