Genetic variants contribute to gene expression variability in humans

Area of Science:

• Genetics
• Genomics
• Systems Biology

Background:

• Expression quantitative trait loci (eQTL) studies link genetic variants to gene expression means.
• Gene expression variability, or variance, has been largely unexplored in relation to genetic variants.

Purpose of the Study:

• To systematically explore genome-wide associations between genetic variants and gene expression variability in humans.
• To identify novel genomic loci, termed expression variability QTL (evQTL), associated with gene expression variance.

Main Methods:

• Adaptation of the double generalized linear model (dglm) to simultaneously model gene expression means and variances.
• Analysis of gene expression data from lymphoblastoid cell lines (LCLs) of 210 HapMap individuals.
• Genome-wide association analysis for both cis- and trans-acting evQTL.

Main Results:

• Identification of cis-acting evQTL for 218 genes, with 8 genes cross-validated.
• Discovery of approximately 300 trans-acting evQTL involving common SNPs and representative genes.
• Exploration of single-SNP and multiple-SNP effects on expression variability.

Conclusions:

• Detecting evQTL provides a novel approach to screen for genetic interactions, particularly those involving multiple SNPs influencing expression variability.
• The findings contribute to understanding the genetic mechanisms underlying gene expression variability.