Abundant Parent-of-origin Effect eQTL: The Framingham Heart Study.

Area of Science:

• Genetics and Genomics
• Molecular Biology
• Bioinformatics

Background:

• Parent-of-origin effect (POE) describes allele inheritance influencing phenotype based on parental origin.
• Previous studies on POE for expression quantitative trait loci (eQTL) are limited.
• Understanding POE is crucial for deciphering gene expression regulation and genetic disease.

Purpose of the Study:

• To systematically investigate the extent of POE in gene expression using whole blood data.
• To identify and characterize parent-specific eQTLs (paternal, maternal, and opposing) in human trios.
• To provide a comprehensive resource of POE eQTLs complementary to existing databases like GTEx.

Main Methods:

• Utilized whole genome sequencing and RNA sequencing data from Framingham Heart Study trios.
• Performed eQTL analysis comparing genotype, paternal, maternal, and joint models.
• Employed Bayes factors to identify and classify POE eQTLs, including opposing effects.

Main Results:

• Identified over 2,000 genes with POE eQTLs, with most not located near known imprinted genes.
• Discovered 99 genes with exclusively opposing eQTLs, significantly enriched for phosphoprotein coding.
• Found enrichment of GWAS hits and drug targets among genes with paternal eQTLs.

Conclusions:

• Demonstrates the widespread prevalence of POE in human gene expression, highlighting regulatory complexity.
• Provides novel explanations for previously observed POE phenomena in diabetes and obesity.
• Recommends caution when using gene expression as a proxy in Mendelian randomization studies.