Download GTEx_Intro_062513

Genotype Tissue Expression
(GTEx) Project
Broad Institute of Harvard and MIT
Laboratory, Data Analysis, and Coordinating Center (LDACC)
June 26, 2013
GTEx goals
Generate public resource with tissuespecific eQTLs and gene and isoform
expression data across multiple human
tissues.
Contribute to understanding of effects of
genetic variation on gene expression and
regulation
Assist in interpretation of disease/trait
GWAS signals
Collect on average 30 tissues per
postmortem donor.
Pilot experiment: 190 donors
Goal: 900 donors within the next 2 years
Dense genotyping (Illumina 5M, Exome
array and imputation) and
RNA-Seq across all tissue samples
NIH funded project
Expression Quantitative Trait Loci
• Ideally test in a disease-specific cell context
• Most human tissue types human samples are very
difficult to obtain
• Large sample sizes are required for statistical power
Slide courtesy of David Deluca
There are 9 Tissues that have sufficient sample numbers (> 80):
Adipose Subcutaneous
Artery Tibial
Heart Left Ventricle
Lung
Muscle Skeletal
Nerve Tibial
Skin Sun Exposed Lower leg
Thyroid
Whole Blood
From GTEx portal documentation
Summary of data generated in GTEx Pilot experiment:
RNA-Seq data on 1,816 tissue samples (.bams and RPKM expression)
Illumina 5M, Exome, and imputed genotypes available on 190 donors
Robust medical history data on all 190 donors
Access to GTEx Pilot data:
GTEx Pilot data (genotypes and RNA-seq) available through the database of Genotypes
and Phenotypes (dbGaP, study accessionphs000424.v3.p1)
Limited access, de-identified datasets are available from GTEx Portal
(http://www.broadinstitute.org/gtex/) under ‘Datasets’ tab.
Can search for expression Quantitative Trait Loci (eQTL) related to your favorite genes
and SNPs and cross-tissue gene expression on the GTEx Portal on the 'Search' tab.
http://www.broadinstitute.org/gtex/
Potential Applications of GTEx in Complex Disease Genetics Studies
Are top GWAS SNP associations enriched for eQTLs for a given tissue of
interest?
Are GWAS signals including more modest ones enriched for eQTLs in a
relevant tissue?
Tissue-specific eQTLs can be used to propose causal gene and tissue
Tissue-specific isoforms can be used to determine which variants are
expressed in relevant tissues – useful for rare variant analysis of
complex traits.