Genetic effects on gene expression across human tissues

被引：2570

作者：

Aguet, Francois ^{[1
]}

Brown, Andrew A. ^{[2
,3
,4
]}

Castel, Stephane E. ^{[5
,6
,15
,16
]}

Davis, Joe R. ^{[5
,6
,7
,8
]}

He, Yuan ^{[9
,35
]}

Jo, Brian ^{[10
,29
]}

Mohammadi, Pejman ^{[5
,6
,15
,16
]}

Park, Yoson ^{[11
]}

Parsana, Princy ^{[8
,12
]}

Segre, Ayellet V. ^{[1
]}

Strober, Benjamin J. ^{[9
,35
]}

Zappala, Zachary ^{[5
,6
,7
,8
]}

Cummings, Beryl B. ^{[1
,2
,13
]}

Gelfand, Ellen T. ^{[1
]}

Hadley, Kane ^{[1
]}

Huang, Katherine H. ^{[1
]}

Lek, Monkol ^{[2
,13
]}

Li, Xiao ^{[5
]}

Nedzel, Jared L. ^{[1
]}

Nguyen, Duyen Y. ^{[1
]}

Noble, Michael S.

Sullivan, Timothy J.

Tukiainen, Taru ^{[2
,13
]}

MacArthur, Daniel G. ^{[1
,2
,13
]}

Getz, Gad ^{[1
,3
,14
]}

Management, Nih Program

Addington, Anjene ^{[15
]}

Guan, Ping ^{[16
,79
]}

Koester, Susan ^{[15
]}

Little, A. Roger ^{[17
,83
]}

Lockhart, Nicole C. ^{[18
]}

Moore, Helen M. ^{[16
,79
]}

Rao, Abhi ^{[16
,79
]}

Struewing, Jeffery P. ^{[19
,81
]}

Volpi, Simona ^{[19
,81
]}

Collection, Biospecimen

Brigham, Lori E. ^{[20
,84
]}

Hasz, Richard ^{[21
,85
]}

Hunter, Marcus ^{[22
,86
]}

Johns, Christopher ^{[23
,87
]}

Johnson, Mark ^{[24
,86
]}

Kopen, Gene ^{[25
,89
]}

Leinweber, William F. ^{[25
,89
]}

Lonsdale, John T. ^{[25
,89
]}

McDonald, Alisa ^{[25
,89
]}

Mestichelli, Bernadette ^{[25
,89
]}

Myer, Kevin ^{[22
,86
]}

Roe, Bryan ^{[22
]}

Salvatore, Michael ^{[25
,89
]}

Shad, Saboor ^{[25
,89
]}

机构：

[1] Harvard Univ, Broad Inst Massachusetts Inst Technol, Cambridge, MA 02142 USA

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

[3] Massachusetts Gen, Massachusetts Gen Hosp, Hosp Canc Ctr & Dept Pathol, Boston, MA 02114 USA

[4] Harvard Med Sch, Dept Genet, Boston, MA 02114 USA

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

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

[7] Ben Gurion Univ Negev, Dept Clin Biochem & Pharmacol, Fac Hlth Sci, Negev, IL-84105 Beer Sheva, Israel

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

[9] Barcelona Inst Sci & Technol, Ctr Genom Regulat CRC, Barcelona 08003, Spain

[10] Univ Pompeu Fabra UPF, Barcelona 08002, Spain

[11] Univ Geneva Med Sch, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland

[12] Univ Geneva, Inst Genet & Genom Geneva iG3, CH-1211 Geneva, Switzerland

[13] Swiss Inst Bioinformat, CH-1211 Geneva, Switzerland

[14] Univ Pennsylvania, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA

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

[16] Columbia Univ rvlecl Ctr, Dept Syst Biol, New York, NY 10032 USA

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

[18] Washington Univ Sch Med, McDonnell Genome Inst, St Louis, MO USA

[19] Washington Univ Sch Med, Dept Genet, St Louis, MO 63108 USA

[20] Washington Univ Sch Med, Dept Pathol Immunol, St Louis, MO 63108 USA

[21] Vanderbilt Univ tvlecl Ctr, Dept tvleclicine, Divis Genet Med, Nashville, TN 37232 USA

[22] Princeton Univ, Dept Comp Sci, Ctr Stat & Machine Learning, Princeton, NJ 08540 USA

[23] Univ Calif Los Angeles, Dept Comp Sci, Los Angeles, CA 90095 USA

[24] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90095 USA

[25] Univ Porto, Inst Investigac Inovac Saucle i3S, P-4200135 Oporto, Portugal

[26] Univ Porto, Inst Mol Pathol & Immunol IPATIMUP, P-4200625 Oporto, Portugal

[27] Univ Amsterdam, Acad Mecl Ctr, Dept Clin Epidemiol, Biostatist & Bioinformat, NL-1105 AZ Amsterdam, Netherlands

[28] Univ Amsterdam, Acad Med Ctr, Dept Psychiat, NL-1105 AZ Amsterdam, Netherlands

[29] Princeton Univ, Lewis Sigler Inst, Princeton, NJ 08540 USA

[30] Princeton Univ, Dept Operat Res & Financial Engn, Princeton, NJ 08540 USA

[31] Stanford Univ, Biomed Informat Program, Stanford, CA 94305 USA

[32] Inst Hosp Mar Investigac Med IMIM, Barcelona 08003, Spain

[33] Washington Univ Sch Med, Dept Med, St Louis, MO 63108 USA

[34] Univ Ulsan Coll Med, Dept Convergence Med, Asan Med Ctr, Seoul 138736, South Korea

[35] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21218 USA

[36] Univ Chicago, Sect Genet Med, Dept Med, Chicago, IL 60637 USA

[37] Columbia Univ, Mailman Sch Publ Hlth, Dept Biostatist, New York, NY 10032 USA

[38] Stanford Univ, Dept Biol, Stanford, CA 94305 USA

[39] Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England

[40] Univ Oxford, Churchill Hosp, Ctr Diabet, Endocrinol & Metab, Oxford 033 7LE, England

[41] Oxford NIHR Biomed Res Ctr, Churchill Hosp, Oxford 0X3 7LJ, England

[42] Duke Univ, Computat Biol Bioinformat Grad Program, Durham, NC 27708 USA

[43] McGill Univ, Human Genet Dept, Montreal, PQ H3A 2T5, Canada

[44] Univ Politecn Cataluna, Dept Estadist Investigac Operat, Barcelona 08034, Spain

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

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

[47] Univ N Carolina, Dept Stat & Operat Res, Chapel Hill, NC 27599 USA

[48] Univ N Carolina, Dept Biostatist, Chapel Hill, NC 27599 USA

[49] Univ Chicago, Inst Genom & Syst Biol, Chicago, IL 60637 USA

[50] Univ Texas MD Anderson Canc Ctr, Dept Biostatist, Houston, TX 77030 USA

来源：

NATURE | 2017年 / 550卷 / 7675期

基金：

美国国家科学基金会; 美国国家卫生研究院;

关键词：

FALSE DISCOVERY RATE; TRANSCRIPTION FACTOR; TRANS-EQTLS; GENOME; VARIANTS; IDENTIFICATION; HYPOTHYROIDISM; ASSOCIATIONS; THOUSANDS; POWER;

D O I：

10.1038/nature24277

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：

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.

引用

页码：204 / +

页数：37

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