This brief overview article [attached] should interest those of you who wish to combine genotype data (DNA mutations) and gene expression (transcriptomics) with human diseases or other traits such as drug efficacy or toxicity (multifactorial traits). Identifying the molecular and cellular basis of human complex disease –– should provide new opportunities for disease prevention and treatment. Genome-wide association studies (GWAS) have already yielded thousands of genetic associations –– localizing regions of the genome that confer increased disease risk. However, within disease-associated regions, causal variants and the mechanism of action often remain poorly understood. To address this challenge, the (previously launched) Genotype-Tissue Expression (GTEx) Project has generated a systematic, multi-tissue reference for identifying genetic variants associated with changes in gene expression (expression quantitative trait loci, eQTLs).
The GTEx resource supports research into potential mechanisms of action for disease-associated variants. Beyond gene expression, a rapidly increasing array of molecular and sequencing-based assays is identifying genetic variants associated with many intermediate molecular phenotypes. Identifying any particular genetic variant’s downstream cascade of effects, from molecule to the individual, requires assaying multiple layers of molecular complexity. Authors [attached] introduce the latest innovation, the Enhancing GTEx (eGTEx) Project –– that extends the GTEx Project by combining gene expression with additional intermediate molecular measurements on the same tissues. These modifications and updates should provide a resource for studying how genetic differences cascade through molecular phenotypes to impact human health.
Nat Genet Dec 2o17; 49: 1664–1669