Interactions between genetic variation and cellular environment in skeletal muscle gene expression

Area of Science:

• Genomics
• Molecular Biology
• Environmental Health

Background:

• Gene expression is influenced by both genetics and environmental factors.
• Understanding genotype-environment interactions (GxE) is crucial for comprehending trait variation.
• RNA-sequencing provides a molecular readout of genetic and environmental influences.

Purpose of the Study:

• To explore the use of allele-specific expression (ASE) for discovering cis-acting genotype-environment interactions (GxE).
• To identify genetic effects on gene expression that are contingent upon specific environmental conditions.
• To investigate GxE effects in human skeletal muscle tissue.

Main Methods:

• Utilized RNA-sequencing data from 267 skeletal muscle biopsies.
• Treated 17 common clinical traits as proxies for the cellular environment.
• Applied allele-specific expression (ASE) analysis to detect genotype-environment interactions (GxE).

Main Results:

• Identified 10 candidate environmental response expression quantitative trait loci (reQTLs).
• Detected signals across 6 different traits, representing 12 unique gene-environment trait pairs.
• Observed significant associations for traits including sex, systolic blood pressure, and LDL cholesterol at a 10% FDR.

Conclusions:

• Allele-specific expression (ASE) is a promising approach for detecting genotype-environment interactions (GxE).
• Replication of GxE signals requires harmonized environmental data and sufficient heterozygote sampling.
• Large-scale human transcriptome datasets and standardized phenotyping are essential for comprehensive discovery and validation.