A Burden of Rare Variants Associated with Extremes of Gene Expression in Human Peripheral Blood

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 enrichment of rare variants at the extremes of expression. After sequencing 2-kb promoter regions of 472 genes in 410 healthy adults, we performed a quadratic regression of rare variant count on bins of peripheral blood transcript abundance from microarrays, summing over ranks of all genes. After adjusting for common eQTLs and the major axes of gene expression covariance, a highly significant excess of variants with minor allele frequency less than 0.05 at both high and low extremes across individuals was observed.

Source: The American Journal of Human Genetics - February 4, 2016 Category: Genetics & Stem Cells Authors: Jing Zhao, Idowu Akinsanmi, Dalia Arafat, T.J. Cradick, Ciaran M. Lee, Samridhi Banskota, Urko M. Marigorta, Gang Bao, Greg Gibson Tags: Article Source Type: research