Gene-gene and gene-environment interactions detected by transcriptome sequence analysis in twins

Area of Science:

• Genetics
• Genomics
• Molecular Biology

Background:

• Understanding gene expression is crucial for deciphering complex disease genetics.
• Allele-specific expression (ASE) measurement is enhanced by RNA sequencing.
• The causes of ASE, particularly the influence of genetic and environmental factors, require further investigation.

Purpose of the Study:

• To quantify the contributions of genetic and environmental factors to allele-specific expression (ASE).
• To investigate the roles of gene × gene (G×G) and gene × environment (G×E) interactions in ASE.
• To propose a comprehensive model for ASE determination.

Main Methods:

• Utilized a twin study design to assess genetic and environmental influences on ASE.
• Employed RNA sequencing for precise gene expression quantification and ASE measurement.
• Developed a model to estimate the contributions of cis and trans genetic effects, as well as environmental factors.

Main Results:

• Identified substantial contributions from gene × gene (G×G) interactions to ASE.
• Found significant effects of gene × environment (G×E) interactions on ASE.
• Demonstrated that while cis genetic variability is necessary for ASE, trans factors and environmental interactions modulate its magnitude.

Conclusions:

• ASE is influenced by a complex interplay of genetic and environmental factors.
• G×G and G×E interactions are critical determinants of ASE.
• A refined model highlights the necessity of cis genetic variation and the modulatory role of trans factors and environmental influences on ASE.