Integrative approaches for large-scale transcriptome-wide association studies

Complex traits” (also called “multifactorial traits”) represent those in which hundreds if not thousands of genes contribute, as well as contribution from epigenetic factors, plus daily bombardment of environmental stimuli (both beneficial and damaging). Many genetic variants influence complex traits by modulating gene expression (i.e. transcription), thereby altering the abundance of one or multiple proteins.

In the attached report, authors introduce a powerful strategy that integrates gene expression measurements with summary association statistics from large-scale genome-wide association (GWA) studies to identify genes whose cis-regulated expression is associated with complex traits. They leveraged expression imputation from genetic data to perform a transcriptome-wide association (TWA) study to identify significant expression-trait associations. Their approaches wre applied to expression data from blood and adipose tissue in a total of ~3,000 individuals.

They imputed gene expression into GWA-study data from more than 900,000 phenotype measurements, which led to their identification of 69 new genes significantly associated with obesity-related traits [body-mass index (BMI), lipid profile, and height). Many of these genes are associated with relevant phenotypes in the Hybrid Mouse Diversity Panel. The authors’ findings showcase the power of integrating genotype, gene expression, and phenotype by which one can gain insights into the genetic basis of complex traits.

 Nat Genet  Mar 2o16; 48: 245–252

This entry was posted in Center for Environmental Genetics. Bookmark the permalink.