The statistical practice of the GTEx Project: from single to multiple tissues

Abstract

Background: The Genotype-Tissue Expression (GTEx) Project has collected genetic and transcriptome profiles from a wide spectrum of tissues in nearly 1,000 ceased individuals, providing an opportunity to study the regulatory roles of genetic variants in transcriptome activities from both cross-tissue and tissue-specific perspectives. Moreover, transcriptome activities (e.g., transcript abundance and alternative splicing) can be treated as mediators between genotype and phenotype to achieve phenotypic alteration. Knowing the genotype associated transcriptome status, researchers can better understand the biological and molecular mechanisms of genetic risk variants in complex traits.

Results: In this article, we first explore the genetic architecture of gene expression traits, and then review recent methods on quantitative trait locus (QTL) and co-expression network analysis. To further exemplify the usage of associations between genotype and transcriptome status, we briefly review methods that either directly or indirectly integrate expression/splicing QTL information in genome-wide association studies (GWASs).

Conclusions: The GTEx Project provides the largest and useful resource to investigate the associations between genotype and transcriptome status. The integration of results from the GTEx Project and existing GWASs further advances our understanding of roles of gene expression changes in bridging both the genetic variants and complex traits.

Graphical abstract

Keywords

the Genotype-Tissue Expression Project / quantitative trait loci (QTL) / transcriptome-wide association studies / genome-wide association studies

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