Genetic effects on gene expression across human tissues

GTEx Consortium

Research output: Contribution to journalArticle

499 Citations (Scopus)

Abstract

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease.

Original languageEnglish (US)
Pages (from-to)204-213
Number of pages10
JournalNature
Volume550
Issue number7675
DOIs
StatePublished - Oct 11 2017
Externally publishedYes

Fingerprint

Gene Expression
Inborn Genetic Diseases
Genes
Organ Specificity
Medical Genetics
Human Genome
Human Body
Genotype

ASJC Scopus subject areas

  • General

Cite this

Genetic effects on gene expression across human tissues. / GTEx Consortium.

In: Nature, Vol. 550, No. 7675, 11.10.2017, p. 204-213.

Research output: Contribution to journalArticle

GTEx Consortium. / Genetic effects on gene expression across human tissues. In: Nature. 2017 ; Vol. 550, No. 7675. pp. 204-213.
@article{6dfb4daef116409dbba0286f9a3ddede,
title = "Genetic effects on gene expression across human tissues",
abstract = "Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease.",
author = "{GTEx Consortium} and Fran{\cc}ois Aguet and Brown, {Andrew A.} and Castel, {Stephane E.} and Davis, {Joe R.} and Yuan He and Brian Jo and Pejman Mohammadi and Park, {Yo Son} and Princy Parsana and Segr{\`e}, {Ayellet V.} and Strober, {Benjamin J.} and Zachary Zappala and Cummings, {Beryl B.} and Gelfand, {Ellen T.} and Kane Hadley and Huang, {Katherine H.} and Monkol Lek and Xiao Li and Nedzel, {Jared L.} and Nguyen, {Duyen Y.} and Noble, {Michael S.} and Sullivan, {Timothy J.} and Taru Tukiainen and MacArthur, {Daniel G.} and Gad Getz and Anjene Addington and Ping Guan and Susan Koester and Little, {A. Roger} and Lockhart, {Nicole C.} and Moore, {Helen M.} and Abhi Rao and Struewing, {Jeffery P.} and Simona Volpi and Brigham, {Lori E.} and Richard Hasz and Marcus Hunter and Christopher Johns and Mark Johnson and Gene Kopen and Leinweber, {William F.} and Lonsdale, {John T.} and Alisa McDonald and Bernadette Mestichelli and Kevin Myer and Bryan Roe and Michael Salvatore and Saboor Shad and Thomas, {Jeffrey A.} and Gerald Quon",
year = "2017",
month = "10",
day = "11",
doi = "10.1038/nature24277",
language = "English (US)",
volume = "550",
pages = "204--213",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7675",

}

TY - JOUR

T1 - Genetic effects on gene expression across human tissues

AU - GTEx Consortium

AU - Aguet, François

AU - Brown, Andrew A.

AU - Castel, Stephane E.

AU - Davis, Joe R.

AU - He, Yuan

AU - Jo, Brian

AU - Mohammadi, Pejman

AU - Park, Yo Son

AU - Parsana, Princy

AU - Segrè, Ayellet V.

AU - Strober, Benjamin J.

AU - Zappala, Zachary

AU - Cummings, Beryl B.

AU - Gelfand, Ellen T.

AU - Hadley, Kane

AU - Huang, Katherine H.

AU - Lek, Monkol

AU - Li, Xiao

AU - Nedzel, Jared L.

AU - Nguyen, Duyen Y.

AU - Noble, Michael S.

AU - Sullivan, Timothy J.

AU - Tukiainen, Taru

AU - MacArthur, Daniel G.

AU - Getz, Gad

AU - Addington, Anjene

AU - Guan, Ping

AU - Koester, Susan

AU - Little, A. Roger

AU - Lockhart, Nicole C.

AU - Moore, Helen M.

AU - Rao, Abhi

AU - Struewing, Jeffery P.

AU - Volpi, Simona

AU - Brigham, Lori E.

AU - Hasz, Richard

AU - Hunter, Marcus

AU - Johns, Christopher

AU - Johnson, Mark

AU - Kopen, Gene

AU - Leinweber, William F.

AU - Lonsdale, John T.

AU - McDonald, Alisa

AU - Mestichelli, Bernadette

AU - Myer, Kevin

AU - Roe, Bryan

AU - Salvatore, Michael

AU - Shad, Saboor

AU - Thomas, Jeffrey A.

AU - Quon, Gerald

PY - 2017/10/11

Y1 - 2017/10/11

N2 - Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease.

AB - Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease.

UR - http://www.scopus.com/inward/record.url?scp=85031313737&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85031313737&partnerID=8YFLogxK

U2 - 10.1038/nature24277

DO - 10.1038/nature24277

M3 - Article

C2 - 29022597

AN - SCOPUS:85031313737

VL - 550

SP - 204

EP - 213

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7675

ER -