genotype tissue expression ( gtex ) project

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Genotype Tissue Expression (GTEx) Project Broad Institute of Harvard and MIT Laboratory, Data Analysis, and Coordinating Center (LDACC) June 26, 2013

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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 tissue-specific eQTLs and gene and isoform expression data across multiple human tissues. - PowerPoint PPT Presentation

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Page 1: Genotype Tissue Expression ( GTEx ) Project

Genotype Tissue Expression (GTEx) Project

Broad Institute of Harvard and MIT

Laboratory, Data Analysis, and Coordinating Center (LDACC)

June 26, 2013

Page 2: Genotype Tissue Expression ( GTEx ) Project

GTEx goals

Generate public resource with tissue-specific 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 donorsGoal: 900 donors within the next 2 years

Dense genotyping (Illumina 5M, Exome array and imputation) andRNA-Seq across all tissue samples

NIH funded project

Page 3: Genotype Tissue Expression ( GTEx ) Project

• 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

Expression Quantitative Trait Loci

Slide courtesy of David Deluca

Page 4: Genotype Tissue Expression ( GTEx ) Project

There are 9 Tissues that have sufficient sample numbers (> 80):Adipose SubcutaneousArtery TibialHeart Left VentricleLungMuscle SkeletalNerve TibialSkin Sun Exposed Lower legThyroidWhole Blood

From GTEx portal documentation

Page 5: Genotype Tissue Expression ( GTEx ) Project

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.

Page 6: Genotype Tissue Expression ( GTEx ) Project

http://www.broadinstitute.org/gtex/

Page 7: Genotype Tissue Expression ( GTEx ) Project
Page 8: Genotype Tissue Expression ( GTEx ) Project

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.