Genetic effects on gene expression across human tissues

TLDR

Characterization of the human genome’s molecular function and its variation across individuals is essential for uncovering the cellular mechanisms underlying human genetic traits and diseases. The GTEx project aims to characterize variation in gene expression across individuals and diverse tissues, and this study describes genetic effects on expression across 44 human tissues. Using GTEx data from 44 tissues, the authors identify genetic effects on expression, then characterize tissue‑specific patterns, compare local and distal effects, and evaluate their functional properties. They find that local genetic variation influences expression of most genes, identify inter‑chromosomal effects for 93 genes and 112 loci, and show that multi‑tissue data can pinpoint disease‑associated genes and pathways, providing mechanistic insight into gene regulation and disease.

Abstract

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease.