Common Fund (CF) Genotype-Tissue Expression Project (GTEx)

Lay Description

The aim of the Genotype-Tissue Expression (GTEx) Project is to increase our understanding of how changes in our genes affect human health and disease with the ultimate goal of improving health care for future generations. GTEx will create a database that researchers can use to study how inherited changes in genes lead to common diseases.

GTEx researchers are studying genes in different tissues obtained from many different people. The GTEx project also includes a study of the GTEx donor consent process - this study will help ensure that the consent process and other aspects of the project effectively address the concerns and expectations of participants in the study. GTEx is a pioneering project that uses state-of-the-art protocols for obtaining and storing a large range of organs and tissues, and for testing them in the lab. Until now, no project has analyzed genetic variation and expression in as many tissues from the same person in such a large population as planned for GTEx.

Scientific Description

Understanding the role of variation in the human genome is crucial to elucidating genetic contributions to human health and disease. Despite the results of genome-wide association studies (GWAS) documenting strong statistical associations between genetic variation and human traits, the functional role for most of these variants is largely unexplained. Nearly 90% of these GWAS-implicated sites lie outside of protein-coding sequences, suggesting that these variants might regulate gene expression.

The goal of the Genotype-Tissue Expression (GTEx) project is to establish a resource database and tissue biobank in which to study the relationship between genetic variation and gene expression and other molecular phenotypes in reference/non-diseased tissues. The ultimate resource will include approximately 960 post-mortem donors with several dozen tissues from each, a resource large enough to study both cis- and trans- gene expression quantitative trait loci (eQTLs). Some tissue will also be banked for additional molecular analyses. To request biosamples, please see the Biobank page for more information.

GTEx was initially funded as a 2-year pilot project by the NIH Common Fund (CF) in 2010, and has been scaled up after demonstration of feasibility. The project will collect and analyze RNA levels in many different human tissues and each donor will be characterized for germline genetic variation through dense genotyping arrays and sequencing of either whole exomes or whole genomes.

By treating RNA expression levels as quantitative traits, eQTLs will be identified as sites containing genetic variation that correlate with changes in RNA expression. Such eQTLs have been associated with 4%-12% of expressed human genes, and with common complex human diseases, including obesity, atherosclerosis, type 2 diabetes, Crohn's disease, and asthma. Additionally, few studies have examined the tissue specificity of eQTLs. A subset of banked tissue samples will also be analyzed for other molecular phenotypes, such as DNA methylation, DNaseI hypersensitivity sites, and proteomics. The GTEx project will thus serve as a resource database and tissue bank for many future studies, especially for understanding the functional basis of inherited susceptibility to disease.

All GTEx releases since Version 5 follow the NIH Genomic Data Sharing (GDS) Policy whereby there are no restrictions on use or publication after release. Additional information about the GTEx Data Release and Publication policy can be found on the GTEx Data Portal at www.gtexportal.org.

• Study Weblinks:
  • NHGRI GTEx
  • GTEx Data Portal
  • caHUB GTEx Sample Collection SOPs
• Study Design:
  • Cross-Sectional
• Study Type:
  • Reference Set
  • Tissue Expression
• dbGaP estimated ancestry using GRAF-pop
• Total number of consented subjects: 983
• Subject Sample Telemetry Report (SSTR)

Donor Inclusion/Exclusion Criteria are as follows:

1. 21 ≤ Age (years) ≤ 70
2. 18.5 < Body Mass Index < 35
3. Time between death and tissue collection less than 24 hours
4. No whole blood transfusion within 48 hours prior to death
5. No history of metastatic cancer
6. No chemotherapy or radiation therapy within the 2 years prior to death
7. Generally unselected for presence or absence of diseases or disorders, except for potentially communicable diseases that disqualify someone to donate organs or tissues would also be disqualifying for GTEx.

June 2008 - GTEx Planning Workshop held in Bethesda, MD
July 2010 - Laboratory, Data Analysis, and Coordinating Center awarded
August 2010 - Biospecimen Source Sites awarded
September 2010 - Statistical methods development R01 awards made
December 2010 - First donor enrolled comparing collection methods
May 2011 - First donors enrolled under full protocol
June 2012 - Initial dbGaP release
November 2012 - "Enhancing GTEx" RFA (RM12-009) published
April 2013 - dbGaP release of "Pilot" data from first 175 donors
June 2013 - First GTEx Community Meeting
August 2013 - New R01 Statistical Methods grants awarded
October 2015 - Release of Midpoint dataset
December 2015 - Donor enrollment completed

• Primary Phenotype: Reference Values

• caHUB Biospecimen Source Site (BSS) - National Disease Research Interchange
  • John Lonsdale. National Disease Research Interchange, Philadelphia, PA, USA.
  • Jeffrey Thomas. National Disease Research Interchange, Philadelphia, PA, USA.
• Funding Source - National Disease Research Interchange
  • X10S170. Leidos Biomedical Research, Inc. (formerly SAIC-Frederick, Inc.), Frederick, MD, USA; National Cancer Institute and Office of the Director, National Institutes of Health, Bethesda, MD, USA.
• caHUB Biospecimen Source Site (BSS) - Roswell Park Cancer Institute
  • Barbara Foster. Roswell Park Cancer Institute, Buffalo, NY, USA.
• Funding Source - Roswell Park Cancer Institute
  • X10S171. Leidos Biomedical Research, Inc. (formerly SAIC-Frederick, Inc.), Frederick, MD, USA; National Cancer Institute and Office of the Director, National Institutes of Health, Bethesda, MD, USA.
• caHUB Biospecimen Source Site (BSS) - Science Care, Inc.
  • Harold Magazine. Science Care, Inc., Phoenix, AZ, USA.
  • Mark Kartub. Science Care, Inc., Phoenix, AZ, USA.
• Funding Source - Science Care, Inc.
  • X10S172. Leidos Biomedical Research, Inc. (formerly SAIC-Frederick, Inc.), Frederick, MD, USA; National Cancer Institute and Office of the Director, National Institutes of Health, Bethesda, MD, USA.
• Laboratory, Data Analysis and Coordinating Center (LDACC)
  • Gad Getz. Broad Institute, Cambridge, MA, USA.
  • Kristin Ardlie. Broad Institute, Cambridge, MA, USA.
• Funding Source - Broad Institute, Inc.
  • HHSN268201000029C. National Heart, Lung, and Blood Institute and Office of the Director, National Institutes of Health, Bethesda, MD, USA.
• Brain Bank (BB)
  • Deborah Mash. University of Miami, Miami, FL, USA.
• Funding Source - Brain Bank Supplement
  • R01 DA006227. National Institute of Drug Abuse, National Institute of Mental Health, and National Institute of Neurological Disorders and Stroke, and Office of the Director, National Institutes of Health, Bethesda, MD, USA.
• caHUB Comprehensive Biospecimen Resource (CBR)
  • Scott Jewell. Van Andel Research Institute, Grand Rapids, MI, USA.
• Funding Source - Comprehensive Biospecimen Resource
  • 10ST1035. Leidos Biomedical Research, Inc. (formerly SAIC-Frederick, Inc.), Frederick, MD, USA; National Cancer Institute and Office of the Director, National Institutes of Health, Bethesda, MD, USA.
• caHUB Comprehensive Data Resource (CDR)
  • Greg Korzeniewski. Leidos Biomedical Research, Inc. (formerly SAIC-Frederick, Inc.), Frederick, MD, USA.
• Funding Source - Comprehensive Data Resource
  • HHSN261200800001E. National Cancer Institute and Office of the Director, National Institutes of Health, Bethesda, MD, USA.
• Statistical Methods Development R01 MH090941
  • Emmanouil Dermitzakis (contact). University of Geneva, Switzerland.
  • Roderic Guigo. Fundacion Privada Centre de Regulacion Genomica (CRG), Barcelona, Spain.
  • Daphne Koller. Stanford University, Palo Alto, CA, USA.
  • Mark McCarthy. University of Oxford, United Kingdom.
• Funding Source - University of Geneva
  • R01 MH090941 "Methods for high-resolution analysis of genetic effects on gene expression". National Institute of Mental Health and Office of the Director, National Institutes of Health, Bethesda, MD, USA.
  • R01 MH101814 "Methods for high-resolution analysis of genetic effects on gene expression". National Institute of Mental Health and Office of the Director, National Institutes of Health, Bethesda, MD, USA.
• Statistical Methods Development R01 MH090951
  • Jonathan Pritchard. University of Chicago, Chicago, IL, USA.
• Funding Source - University of Chicago (Pritchard)
  • R01 MH090951 "Statistical analysis of gene expression quantitative trait loci (eQTL)". National Institute of Mental Health and Office of the Director, National Institutes of Health, Bethesda, MD, USA.
• Statistical Methods Development R01 MH090937
  • Nancy Cox (contact). University of Chicago, Chicago, IL, USA.
  • Dan Nicolae. University of Chicago, Chicago, IL, USA.
• Funding Source - University of Chicago (Cox)
  • R01 MH090937 "Using the Transcriptome for SNP and Gene Annotation". National Institute of Mental Health, National Human Genome Research Institute, National Heart Lung and Blood Institute and Office of the Director, National Institutes of Health, Bethesda, MD, USA.
  • R01 MH101820 "Harnessing GTEx to create transcriptome knowledge and inform disease biology". National Institute of Mental Health and Office of the Director, National Institutes of Health, Bethesda, MD, USA.
• Statistical Methods Development R01 MH090936
  • Ivan Rusyn (contact). University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Andrew Nobel. University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Fred Wright. University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
• Funding Source - University of North Carolina, Chapel Hill
  • R01 MH090936 "Facilitating GTEx, Disease, and GxE Analyses via Fast Expression (e)QTL Mapping". National Institute of Mental Health and Office of the Director, National Institutes of Health, Bethesda, MD, USA.
• Statistical Methods Development R01 MH090948
  • Jun Liu. Harvard University, Cambridge, MA, USA.
• Funding Source - Harvard University
  • R01 MH090952 "Epistatic and Cross Tissue Analysis for Human Gene Expression Traits". National Institute of Mental Health, National Human Genome Research Institute and Office of the Director, National Institutes of Health, Bethesda, MD, USA.
• Systems Approaches for Analyzing GTEx R01 MH101782
  • Chiara Sabatti. Stanford University, Palo Alto, CA, USA.
• Funding Source - Stanford University
  • R01 MH101782 "Genetic Regulation of Gene Expression and its Impact on Phenotypes". National Institute of Mental Health and Office of the Director, National Institutes of Health, Bethesda, MD, USA.
• Systems Approaches for Analyzing GTEx R01 MH101810
  • Donald Conrad. Washington University, St Louis, MO, USA.
• Funding Source - Washington University
  • R01 MH101810 "Modeling the effects of structural variation in GTEx data and mendelian disease". National Institute of Mental Health and Office of the Director, National Institutes of Health, Bethesda, MD, USA.
• Systems Approaches for Analyzing GTEx R01 MH101814
  • Emmanouil Dermitzakis (contact). University of Geneva, Switzerland.
  • Carlos Bustamante. Stanford University, Palo Alto, CA, USA.
  • Roderic Guigo. Fundacion Privada Centre de Regulacion Genomica (CRG), Barcelona, Spain.
  • Mark McCarthy. University of Oxford, United Kingdom.
• Systems Approaches for Analyzing GTEx R01 MH101819
  • Fred Wright (contact). North Carolina State University, Raleigh, NC, USA.
  • Andrew Nobel. University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
• Funding Source - North Carolina State University
  • R01 MH101819 "Systems approaches to link tissue-specific expression to disease". National Institute of Mental Health and Office of the Director, National Institutes of Health, Bethesda, MD, USA.
• Systems Approaches for Analyzing GTEx R01 MH101820
  • Nancy Cox (contact). University of Chicago, Chicago, IL, USA.
  • Dan Nicolae. University of Chicago, Chicago, IL, USA.
• Systems Approaches for Analyzing GTEx R01 MH101822
  • Christopher Brown (contact). University of Pennsylvania, Philadelphia, PA, USA.
  • Barbara Engelhardt. Duke University, Durham, NC, USA.
• Funding Source - University of Pennsylvania
  • R01 MH101822 "Identification and validation of cell specific eQTLs by Bayesian modeling". National Institute of Mental Health and Office of the Director, National Institutes of Health, Bethesda, MD, USA.
• Systems Approaches for Analyzing GTEx R01 MH101825
  • Matthew Stephens. University of Chicago, Chicago, IL, USA.
• Funding Source - University of Chicago (Stephens)
  • R01 MH101825 "Statistical analysis of gene expression quantitative trait loci (eQTL)". National Institute of Mental Health and Office of the Director, National Institutes of Health, Bethesda, MD, USA.