The GTEx Consortium atlas of genetic regulatory effects across human tissues

被引：2787

作者：

Aguet, Francois ^{[1
]}

Barbeira, Alvaro N. ^{[2
]}

Bonazzola, Rodrigo ^{[2
]}

Brown, Andrew ^{[3
,4
]}

Castel, Stephane E. ^{[5
,6
]}

Jo, Brian ^{[7
,8
]}

Kasela, Silva ^{[5
,6
]}

Kim-Hellmuth, Sarah ^{[5
,6
,9
]}

Liang, Yanyu ^{[2
]}

Parsana, Princy ^{[11
]}

Flynn, Elise ^{[5
,6
]}

Fresard, Laure ^{[12
]}

Gamazon, Eric R. ^{[13
,14
,15
,16
]}

Hamel, Andrew R. ^{[1
,17
]}

He, Yuan ^{[18
]}

Hormozdiari, Farhad ^{[1
,19
]}

Mohammadi, Pejman ^{[5
,6
,20
,21
]}

Munoz-Aguirre, Manuel ^{[22
,23
]}

Ardlie, Kristin G. ^{[1
]}

Battle, Alexis ^{[11
,18
]}

Bonazzola, Rodrigo ^{[2
]}

Brown, Christopher D. ^{[24
]}

Cox, Nancy ^{[16
]}

Dermitzakis, Emmanouil T. ^{[3
,27
,28
]}

Engelhardt, Barbara E. ^{[7
,8
]}

Garrido-Martin, Diego ^{[22
]}

Gay, Nicole R. ^{[29
]}

Getz, Gad ^{[1
,30
,31
,32
]}

Guigo, Roderic ^{[22
,32
,33
,34
]}

Hamel, Andrew R. ^{[1
,17
]}

Handsaker, Robert E. ^{[33
,34
,35
,36
]}

He, Yuan ^{[18
]}

Hoffman, Paul J. ^{[5
]}

Hormozdiari, Farhad ^{[1
,19
]}

Im, Hae Kyung ^{[2
]}

Jo, Brian ^{[7
,8
]}

Kasela, Silva ^{[5
,6
]}

Kashin, Seva ^{[33
,34
,35
,36
]}

Kim-Hellmuth, Sarah ^{[5
,6
,9
]}

Kwong, Alan ^{[26
]}

Lappalainen, Tuuli ^{[5
,6
]}

Li, Xiao ^{[1
]}

Liang, Yanyu ^{[2
]}

MacArthur, Daniel G. ^{[34
,35
,36
,37
]}

Mohammadi, Pejman ^{[5
,6
,20
,21
]}

Montgomery, Stephen B. ^{[12
,29
]}

Munoz-Aguirre, Manuel ^{[22
,23
]}

Rouhana, John M. ^{[1
,17
]}

Hormozdiari, Farhad ^{[1
,19
]}

Im, Hae Kyung ^{[2
]}

机构：

[1] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[2] Univ Chicago, Dept Med, Sect Genet Med, 5841 S Maryland Ave, Chicago, IL 60637 USA

[3] Univ Geneva, Dept Genet Med & Dev, Med Sch, Geneva, Switzerland

[4] Univ Dundee, Populat Hlth & Genom, Dundee, Scotland

[5] New York Genome Ctr, New York, NY 10013 USA

[6] Columbia Univ, Dept Syst Biol, New York, NY 10027 USA

[7] Princeton Univ, Dept Comp Sci, Princeton, NJ 08544 USA

[8] Princeton Univ, Ctr Stat & Machine Learning, Princeton, NJ 08544 USA

[9] Max Planck Inst Psychiat, Stat Genet, Munich, Germany

[10] Univ Chicago, Dept Publ Hlth Sci, Chicago, IL 60637 USA

[11] Johns Hopkins Univ, Dept Comp Sci, Baltimore, MD 21218 USA

[12] Stanford Univ, Dept Pathol, Stanford, CA 94305 USA

[13] Vanderbilt Univ, Data Sci Inst, Nashville, TN USA

[14] Univ Cambridge, Clare Hall, Cambridge, England

[15] Univ Cambridge, MRC Epidemiol Unit, Cambridge, England

[16] Vanderbilt Univ, Med Ctr, Dept Med, Div Genet Med, Nashville, TN USA

[17] Harvard Med Sch, Massachusetts Eye & Ear, Ocular Genom Inst, Boston, MA 02115 USA

[18] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD USA

[19] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA

[20] Scripps Res Translat Inst, La Jolla, CA USA

[21] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA USA

[22] Barcelona Inst Sci & Technol, Ctr Genom Regulat CRG, Barcelona, Catalonia, Spain

[23] Univ Politecn Catalunya UPC, Dept Stat & Operat Res, Barcelona, Catalonia, Spain

[24] Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA

[25] Univ Penn, Dept Syst Pharmacol & Translat Therapeut, Perelman Sch Med, Philadelphia, PA 19104 USA

[26] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA

[27] Univ Geneva, Inst Genet & Genom Geneva iGE3, Geneva, Switzerland

[28] Swiss Inst Bioinformat, Geneva, Switzerland

[29] Stanford Univ, Dept Genet, Stanford, CA 94305 USA

[30] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA

[31] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA

[32] Harvard Med Sch, Boston, MA 02115 USA

[33] Univ Pompeu Fabra UPF, Barcelona, Catalonia, Spain

[34] Harvard Med Sch, Dept Genet, Boston, MA 02115 USA

[35] Broad Inst MIT & Harvard Univ, Program Med & Populat Genet, Cambridge, MA USA

[36] Broad Inst, Stanley Ctr Psychiat Res, Cambridge, MA USA

[37] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA

[38] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA

[39] Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England

[40] Univ Chicago, Dept Stat, Chicago, IL 60637 USA

[41] Univ Calif Los Angeles, Dept Biomath, Los Angeles, CA USA

[42] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA

[43] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Div Genet, Portland, OR 97201 USA

[44] Univ Calif Los Angeles, Dept Comp Sci, Los Angeles, CA 90024 USA

[45] Stanford Univ, Program Biomed Informat, Sch Med, Stanford, CA USA

[46] MIT, Comp Sci & Artificial Intelligence Lab, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[47] Univ Southern Calif, Sch Pharm, Dept Clin Pharm, Los Angeles, CA USA

[48] Univ N Carolina, Dept Stat & Operat Res, Chapel Hill, NC USA

[49] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27515 USA

[50] Univ Barcelona, Dept Genet Microbiol & Stat, Barcelona, Spain

来源：

SCIENCE | 2020年 / 369卷 / 6509期

基金：

欧盟地平线“2020”; 瑞士国家科学基金会; 美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; LINKAGE DISEQUILIBRIUM; RNA-SEQ; CANCER SUSCEPTIBILITY; ALLELIC HETEROGENEITY; CAUSAL VARIANTS; COMPLEX TRAITS; TRANS-EQTLS; EXPRESSION; LOCI;

D O I：

10.1126/science.aaz1776

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The Genotype-Tissue Expression (GTEx) project was established to characterize genetic effects on the transcriptome across human tissues and to link these regulatory mechanisms to trait and disease associations. Here, we present analyses of the version 8 data, examining 15,201 RNA-sequencing samples from 49 tissues of 838 postmortem donors. We comprehensively characterize genetic associations for gene expression and splicing in cis and trans, showing that regulatory associations are found for almost all genes, and describe the underlying molecular mechanisms and their contribution to allelic heterogeneity and pleiotropy of complex traits. Leveraging the large diversity of tissues, we provide insights into the tissue specificity of genetic effects and show that cell type composition is a key factor in understanding gene regulatory mechanisms in human tissues.

引用

页码：1318 / 1330

页数：13

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