Collection

The Genotype-Tissue Expression project

A more personal gene expression catalogue

We meet a new frontier in biomedical research with publications from the Genotype-Tissue Expression (GTEx) Consortium, that of cataloguing genetic variation and its influence on gene expression within and between all major tissues in the human body. The GTEx project was proposed in 2008 with the lofty goals of establishing a resource database and associated tissue biobank to study the relationship between genetic variation and gene expression in all major human tissues across 1000 individuals. This nearly decade long effort now brings the largest multi-tissue research study using postmortem donors, which entailed overcoming many challenges including developing protocols to obtain high quality biospecimens as well as establishing a framework for the ethical, legal and social issues surrounding postmortem donation.

In this second phase of the project, GTEx profiles genetic variation, gene expression, histological and clinical data for 449 human donors across 44 tissues. The authors use the GTEx data to analyze the influence of genetic variation on gene expression within and between tissues and individuals. These studies have helped to crack the regulatory code of our genome, demonstrating that the expression of nearly all genes are regulated by genetic variation, most of which is located close to the affected gene.

We are pleased to present this Nature collection of news, commentary and research publications across Nature journals and Genome Research for the second phase of the GTEx project. 
 
- Orli Bahcall, Senior Editor,  Nature
 
 
Listen to GTEx researchers discuss the challenges in establishing the GTEx project, including a framework for research on tissues from postmortem donors. Hear from grieving family members about their experience in contributing to this this genetics project. This and more on our Nature  Podcast

News & Commentary

  • Nature Genetics | Commentary | open

    • John Lonsdale
    • , Jeffrey Thomas
    • , Mike Salvatore
    • , Rebecca Phillips
    • , Edmund Lo
    • , Saboor Shad
    • , Richard Hasz
    • , Gary Walters
    • , Fernando Garcia
    • , Nancy Young
    • , Barbara Foster
    • , Mike Moser
    • , Ellen Karasik
    • , Bryan Gillard
    • , Kimberley Ramsey
    • , Susan Sullivan
    • , Jason Bridge
    • , Harold Magazine
    • , John Syron
    • , Johnelle Fleming
    • , Laura Siminoff
    • , Heather Traino
    • , Maghboeba Mosavel
    • , Laura Barker
    • , Scott Jewell
    • , Dan Rohrer
    • , Dan Maxim
    • , Dana Filkins
    • , Philip Harbach
    • , Eddie Cortadillo
    • , Bree Berghuis
    • , Lisa Turner
    • , Eric Hudson
    • , Kristin Feenstra
    • , Leslie Sobin
    • , James Robb
    • , Phillip Branton
    • , Greg Korzeniewski
    • , Charles Shive
    • , David Tabor
    • , Liqun Qi
    • , Kevin Groch
    • , Sreenath Nampally
    • , Steve Buia
    • , Angela Zimmerman
    • , Anna Smith
    • , Robin Burges
    • , Karna Robinson
    • , Kim Valentino
    • , Deborah Bradbury
    • , Mark Cosentino
    • , Norma Diaz-Mayoral
    • , Mary Kennedy
    • , Theresa Engel
    • , Penelope Williams
    • , Kenyon Erickson
    • , Kristin Ardlie
    • , Wendy Winckler
    • , Gad Getz
    • , David DeLuca
    • , Daniel MacArthur
    • , Manolis Kellis
    • , Alexander Thomson
    • , Taylor Young
    • , Ellen Gelfand
    • , Molly Donovan
    • , Yan Meng
    • , George Grant
    • , Deborah Mash
    • , Yvonne Marcus
    • , Margaret Basile
    • , Jun Liu
    • , Jun Zhu
    • , Zhidong Tu
    • , Nancy J Cox
    • , Dan L Nicolae
    • , Eric R Gamazon
    • , Hae Kyung Im
    • , Anuar Konkashbaev
    • , Jonathan Pritchard
    • , Matthew Stevens
    • , Timothèe Flutre
    • , Xiaoquan Wen
    • , Emmanouil T Dermitzakis
    • , Tuuli Lappalainen
    • , Roderic Guigo
    • , Jean Monlong
    • , Michael Sammeth
    • , Daphne Koller
    • , Alexis Battle
    • , Sara Mostafavi
    • , Mark McCarthy
    • , Manual Rivas
    • , Julian Maller
    • , Ivan Rusyn
    • , Andrew Nobel
    • , Fred Wright
    • , Andrey Shabalin
    • , Mike Feolo
    • , Nataliya Sharopova
    • , Anne Sturcke
    • , Justin Paschal
    • , James M Anderson
    • , Elizabeth L Wilder
    • , Leslie K Derr
    • , Eric D Green
    • , Jeffery P Struewing
    • , Gary Temple
    • , Simona Volpi
    • , Joy T Boyer
    • , Elizabeth J Thomson
    • , Mark S Guyer
    • , Cathy Ng
    • , Assya Abdallah
    • , Deborah Colantuoni
    • , Thomas R Insel
    • , Susan E Koester
    • , A Roger Little
    • , Patrick K Bender
    • , Thomas Lehner
    • , Yin Yao
    • , Carolyn C Compton
    • , Jimmie B Vaught
    • , Sherilyn Sawyer
    • , Nicole C Lockhart
    • , Joanne Demchok
    •  &  Helen F Moore
  • Nature Genetics | Commentary

    • eGTEx Project
    • , Barbara E Stranger
    • , Lori E Brigham
    • , Richard Hasz
    • , Marcus Hunter
    • , Christopher Johns
    • , Mark Johnson
    • , Gene Kopen
    • , William F Leinweber
    • , John T Lonsdale
    • , Alisa McDonald
    • , Bernadette Mestichelli
    • , Kevin Myer
    • , Brian Roe
    • , Michael Salvatore
    • , Saboor Shad
    • , Jeffrey A Thomas
    • , Gary Walters
    • , Michael Washington
    • , Joseph Wheeler
    • , Jason Bridge
    • , Barbara A Foster
    • , Bryan M Gillard
    • , Ellen Karasik
    • , Rachna Kumar
    • , Mark Miklos
    • , Michael T Moser
    • , Scott D Jewell
    • , Robert G Montroy
    • , Daniel C Rohrer
    • , Dana R Valley
    • , David A Davis
    • , Deborah C Mash
    • , Sarah E Gould
    • , Ping Guan
    • , Susan Koester
    • , A Roger Little
    • , Casey Martin
    • , Helen M Moore
    • , Abhi Rao
    • , Jeffery P Struewing
    • , Simona Volpi
    • , Kasper D Hansen
    • , Peter F Hickey
    • , Lindsay F Rizzardi
    • , Lei Hou
    • , Yaping Liu
    • , Benoit Molinie
    • , Yongjin Park
    • , Nicola Rinaldi
    • , Li Wang
    • , Nicholas Van Wittenberghe
    • , Melina Claussnitzer
    • , Ellen T Gelfand
    • , Qin Li
    • , Sandra Linder
    • , Rui Zhang
    • , Kevin S Smith
    • , Emily K Tsang
    • , Lin S Chen
    • , Kathryn Demanelis
    • , Jennifer A Doherty
    • , Farzana Jasmine
    • , Muhammad G Kibriya
    • , Lihua Jiang
    • , Shin Lin
    • , Meng Wang
    • , Ruiqi Jian
    • , Xiao Li
    • , Joanne Chan
    • , Daniel Bates
    • , Morgan Diegel
    • , Jessica Halow
    • , Eric Haugen
    • , Audra Johnson
    • , Rajinder Kaul
    • , Kristen Lee
    • , Matthew T Maurano
    • , Jemma Nelson
    • , Fidencio J Neri
    • , Richard Sandstrom
    • , Marian S Fernando
    • , Caroline Linke
    • , Meritxell Oliva
    • , Andrew Skol
    • , Fan Wu
    • , Joshua M Akey
    • , Andrew P Feinberg
    • , Jin Billy Li
    • , Brandon L Pierce
    • , John A Stamatoyannopoulos
    • , Hua Tang
    • , Kristin G Ardlie
    • , Manolis Kellis
    • , Michael P Snyder
    •  &  Stephen B Montgomery

Research

  • Nature | Letter | open

    The authors show that rare genetic variants contribute to large gene expression changes across diverse human tissues and provide an integrative method for interpretation of rare variants in individual genomes.

    • Xin Li
    • , Yungil Kim
    • , Emily K. Tsang
    • , Joe R. Davis
    • , Farhan N. Damani
    • , Colby Chiang
    • , Gaelen T. Hess
    • , Zachary Zappala
    • , Benjamin J. Strober
    • , Alexandra J. Scott
    • , Amy Li
    • , Andrea Ganna
    • , Michael C. Bassik
    • , Jason D. Merker
    • , GTEx Consortium
    • , Ira M. Hall
    • , Alexis Battle
    •  &  Stephen B. Montgomery
  • Nature | Letter | open

    Multiple transcriptome approaches, including single-cell sequencing, demonstrate that escape from X chromosome inactivation is widespread and occasionally variable between cells, chromosomes, and tissues, resulting in sex-biased expression of at least 60 genes and potentially contributing to sex-specific differences in health and disease.

    • Taru Tukiainen
    • , Alexandra-Chloé Villani
    • , Angela Yen
    • , Manuel A. Rivas
    • , Jamie L. Marshall
    • , Rahul Satija
    • , Matt Aguirre
    • , Laura Gauthier
    • , Mark Fleharty
    • , Andrew Kirby
    • , Beryl B. Cummings
    • , Stephane E. Castel
    • , Konrad J. Karczewski
    • , François Aguet
    • , Andrea Byrnes
    • , GTEx Consortium
    • , Tuuli Lappalainen
    • , Aviv Regev
    • , Kristin G. Ardlie
    • , Nir Hacohen
    •  &  Daniel G. MacArthur
  • Nature | Letter

    Using the GTEx data and others, a comprehensive analysis of adenosine-to-inosine RNA editing in mammals is presented; targets of the various ADAR enzymes are identified, as are several potential regulators of editing, such as AIMP2.

    • Meng How Tan
    • , Qin Li
    • , Raghuvaran Shanmugam
    • , Robert Piskol
    • , Jennefer Kohler
    • , Amy N. Young
    • , Kaiwen Ivy Liu
    • , Rui Zhang
    • , Gokul Ramaswami
    • , Kentaro Ariyoshi
    • , Ankita Gupte
    • , Liam P. Keegan
    • , Cyril X. George
    • , Avinash Ramu
    • , Ni Huang
    • , Elizabeth A. Pollina
    • , Dena S. Leeman
    • , Alessandra Rustighi
    • , Y. P. Sharon Goh
    • , GTEx Consortium
    • , Ajay Chawla
    • , Giannino Del Sal
    • , Gary Peltz
    • , Anne Brunet
    • , Donald F. Conrad
    • , Charles E. Samuel
    • , Mary A. O’Connell
    • , Carl R. Walkley
    • , Kazuko Nishikura
    •  &  Jin Billy Li
  • Nature Genetics | Article

    Ira Hall, Donald Conrad, the GTEx consortium and colleagues identify 23,602 high-confidence structural variants (SVs) and 24,884 cis expression quantitative trait loci (eQTLs) across 13 human tissues. They estimate that SVs are the causal variant at 3.5–6.8% of eQTLs and identify 789 SVs predicted to directly alter gene expression, most of which are noncoding variants in regulatory elements.

    • Colby Chiang
    • , Alexandra J Scott
    • , Joe R Davis
    • , Emily K Tsang
    • , Xin Li
    • , Yungil Kim
    • , Tarik Hadzic
    • , Farhan N Damani
    • , Liron Ganel
    • , GTEx Consortium
    • , Stephen B Montgomery
    • , Alexis Battle
    • , Donald F Conrad
    •  &  Ira M Hall

Methods publications

  • Nature Genetics | Technical Report

    Hae Kyung Im and colleagues report a method for predicting gene expression perturbations from genotype data after training on reference transcriptome data sets. Association of predicted gene expression with disease traits identifies known and new candidate disease genes.

    • Eric R Gamazon
    • , Heather E Wheeler
    • , Kaanan P Shah
    • , Sahar V Mozaffari
    • , Keston Aquino-Michaels
    • , Robert J Carroll
    • , Anne E Eyler
    • , Joshua C Denny
    • , GTEx Consortium
    • , Dan L Nicolae
    • , Nancy J Cox
    •  &  Hae Kyung Im
  • Nature Methods | Brief Communication

    The EAGLE algorithm and software identifies replicable gene-by-environment interactions based on associations between environment and allele-specific expression.

    • David A Knowles
    • , Joe R Davis
    • , Hilary Edgington
    • , Anil Raj
    • , Marie-Julie Favé
    • , Xiaowei Zhu
    • , James B Potash
    • , Myrna M Weissman
    • , Jianxin Shi
    • , Douglas F Levinson
    • , Philip Awadalla
    • , Sara Mostafavi
    • , Stephen B Montgomery
    •  &  Alexis Battle
  • Nature Communications | Article | open

    Genome interpretation and analysis of allelic activity requires appropriate haplotype phasing. Here the authors present phASER, a fast and accurate method for variant phrasing from RNA-seq and genome sequencing data.

    • Stephane E. Castel
    • , Pejman Mohammadi
    • , Wendy K. Chung
    • , Yufeng Shen
    •  &  Tuuli Lappalainen