Thursday, March 21, 2019

BISTRO - Li Guan

4:00 PM

2036 Palmer Commons

Weekly Bioinformatics Student Research Presentations

"Genetic regulation of mRNA and miRNA expression across two human tissues and its relationship to complex traits"

Abstract

Genetic variation has a substantial impact on transcript abundance. Genetic variants that influence transcript abundance are known as expression quantitative trait loci (eQTLs). eQTLs are of great interest because the resulting changes in gene expression can partially explain the phenotypic variation across individuals. To date most QTL studies of gene expression in human tissues have focused on mRNA, little is known about microRNA (miRNA). To study the genetic regulation of mRNA and miRNA expression and its relationship to complex traits, we performed genotyping, mRNA-seq and miRNA-seq from skeletal muscle and subcutaneous adipose biopsies of the same Finnish individuals.

At 5% FDR, we identified 26.7% of tested miRNA in muscle and 25.0% in adipose had at least 1 eQTL, smaller percentages than observed for mRNA (86.5% in muscle and 84.7% in adipose). The vast majority (96.7% for mRNA and 100% for miRNA) of eQTLs that were significant in both tissues displayed consistent direction of effects. We leveraged the discovered QTLs to understand the biological basis of genome-wide association findings for a range of complex traits using a Mendelian randomization technique. We identified thousands of mRNAs and tens of miRNAs in each tissue that may drive the genetic associations for complex traits.

The results add to our understanding of genetic regulation in human skeletal muscle and subcutaneous adipose and provide insight into the potential biological mechanisms underlying the genetic variants associated with complex traits.