Identification of rare and common regulatory variants in pluripotent cells using population-scale transcriptomics

被引：39

作者：

Bonder, Marc Jan ^{[1
,2
,3
]}

Smail, Craig ^{[4
,5
,6
]}

Gloudemans, Michael J. ^{[4
]}

Fresard, Laure ^{[7
]}

Jakubosky, David ^{[8
,9
]}

D'Antonio, Matteo ^{[10
,11
]}

Li, Xin ^{[12
]}

Ferraro, Nicole M. ^{[4
]}

Carcamo-Orive, Ivan ^{[13
]}

Mirauta, Bogdan ^{[1
]}

Seaton, Daniel D. ^{[1
]}

Cai, Na ^{[1
,14
,15
]}

Vakili, Dara ^{[16
,17
]}

Horta, Danilo ^{[1
]}

Zhao, Chunli ^{[18
]}

Zastrow, Diane B. ^{[18
]}

Bonner, Devon E. ^{[18
]}

Wheeler, Matthew T. ^{[13
,18
]}

Kilpinen, Helena ^{[14
,16
,19
,20
]}

Knowles, Joshua W. ^{[13
]}

Smith, Erin N. ^{[21
]}

Frazer, Kelly A. ^{[10
,11
,21
]}

Montgomery, Stephen B. ^{[7
,22
]}

Stegle, Oliver ^{[1
,2
,3
,14
]}

机构：

[1] European Mol Biol Lab, European Bioinformat Inst, Wellcome Trust Genome Campus, Cambridge, England

[2] European Mol Biol Lab, Genome Biol Unit, Heidelberg, Germany

[3] German Canc Res Ctr, Div Computat Genom & Syst Genet, Heidelberg, Germany

[4] Stanford Univ, Dept Biomed Data Sci, Sch Med, Stanford, CA 94305 USA

[5] Childrens Mercy Res Inst, Genom Med Ctr, Kansas City, MO 64108 USA

[6] Childrens Mercy Kansas City, Kansas City, MO 64108 USA

[7] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA

[8] Univ Calif San Diego, Biomed Sci Grad Program, La Jolla, CA 92093 USA

[9] Univ Calif San Diego, Dept Biomed Informat, La Jolla, CA 92093 USA

[10] Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA

[11] Univ Calif San Diego, Rady Childrens Hosp, La Jolla, CA 92093 USA

[12] Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Nutr & Hlth, CAS Key Lab Computat Biol, Shanghai, Peoples R China

[13] Stanford Univ, Div Cardiovasc Med, Sch Med, Stanford, CA 94305 USA

[14] Wellcome Sanger Inst, Wellcome Trust Genome Campus, Cambridge, England

[15] Helmholtz Zentrum Munchen, Helmholtz Pioneer Campus, Neuherberg, Germany

[16] UCL, UCL Great Ormond St Inst Child Hlth, London, England

[17] Imperial Coll London, Fac Med, London, England

[18] Stanford Univ, Stanford Ctr Undiagnosed Dis, Stanford, CA 94305 USA

[19] Univ Helsinki, Fac Biol & Environm Sci, Helsinki, Finland

[20] Univ Helsinki, Helsinki Inst Life Sci HiLIFE, Helsinki, Finland

[21] Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA

[22] Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA

来源：

NATURE GENETICS | 2021年 / 53卷 / 03期

基金：

英国惠康基金; 英国医学研究理事会; 中国国家自然科学基金; 国家重点研发计划; 美国国家卫生研究院; 美国国家科学基金会;

关键词：

GENE-EXPRESSION; FUNCTIONAL VARIATION; SUSCEPTIBILITY LOCI; REVEALS; METAANALYSIS; ASSOCIATION; PROVIDES; BURDEN; IMPACT; GWAS;

D O I：

10.1038/s41588-021-00800-7

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Induced pluripotent stem cells (iPSCs) are an established cellular system to study the impact of genetic variants in derived cell types and developmental contexts. However, in their pluripotent state, the disease impact of genetic variants is less well known. Here, we integrate data from 1,367 human iPSC lines to comprehensively map common and rare regulatory variants in human pluripotent cells. Using this population-scale resource, we report hundreds of new colocalization events for human traits specific to iPSCs, and find increased power to identify rare regulatory variants compared with somatic tissues. Finally, we demonstrate how iPSCs enable the identification of causal genes for rare diseases.

引用

页码：313 / +

页数：22

共 69 条

[11]

Consortium G. P., 2015, NATURE, V526, P68, DOI [DOI 10.1038/NATURE15393, 10.1038/nature15393]

[12] Improving genetic diagnosis in Mendelian disease with transcriptome sequencing [J].

Cummings, Beryl B. ;

Marshall, Jamie L. ;

Tukiainen, Taru ;

Lek, Monkol ;

Donkervoort, Sandra ;

Foley, A. Reghan ;

Bolduc, Veronique ;

Waddell, Leigh B. ;

Sandaradura, Sarah A. ;

O'Grady, Gina L. ;

Estrella, Elicia ;

Reddy, Hemakumar M. ;

Zhao, Fengmei ;

Weisburd, Ben ;

Karczewski, Konrad J. ;

O'Donnell-Luria, Anne H. ;

Birnbaum, Daniel ;

Sarkozy, Anna ;

Hu, Ying ;

Gonorazky, Hernan ;

Claeys, Kristl ;

Joshi, Himanshu ;

Bournazos, Adam ;

Oates, Emily C. ;

Ghaoui, Roula ;

Davis, Mark R. ;

Laing, Nigel G. ;

Topf, Ana ;

Kang, Peter B. ;

Beggs, Alan H. ;

North, Kathryn N. ;

Straub, Volker ;

Dowling, James J. ;

Muntoni, Francesco ;

Clarke, Nigel F. ;

Cooper, Sandra T. ;

Bonnemann, Carsten G. ;

MacArthur, Daniel G. .

SCIENCE TRANSLATIONAL MEDICINE, 2017, 9 (386)

[13]

Cuomo ASE, 2020, NAT COMMUN, V11, DOI 10.1038/s41467-020-14457-z

[14] Insights into the Mutational Burden of Human Induced Pluripotent Stem Cells from an Integrative Multi-Omics Approach [J].

D'Antonio, Matteo ;

Benaglio, Paola ;

Jakubosky, David ;

Greenwald, William W. ;

Matsui, Hiroko ;

Donovan, Margaret K. R. ;

Li, He ;

Smith, Erin N. ;

D'Antonio-Chronowska, Agnieszka ;

Frazer, Kelly A. .

CELL REPORTS, 2018, 24 (04) :883-894

[15] Large-Scale Profiling Reveals the Influence of Genetic Variation on Gene Expression in Human Induced Pluripotent Stem Cells [J].

DeBoever, Christopher ;

Li, He ;

Jakubosky, David ;

Benaglio, Paola ;

Reyna, Joaquin ;

Olson, Katrina M. ;

Huang, Hui ;

Biggs, William ;

Sandoval, Efren ;

D'Antonio, Matteo ;

Jepsen, Kristen ;

Matsui, Hiroko ;

Arias, Angelo ;

Ren, Bing ;

Nariai, Naoki ;

Smith, Erin N. ;

D'Antonio-Chronowska, Agnieszka ;

Farley, Emma K. ;

Frazer, Kelly A. .

CELL STEM CELL, 2017, 20 (04) :533-+

[16] Cellular deconvolution of GTEx tissues powers discovery of disease and cell-type associated regulatory variants [J].

Donovan, Margaret K. R. ;

D'Antonio-Chronowska, Agnieszka ;

D'Antonio, Matteo ;

Frazer, Kelly A. .

NATURE COMMUNICATIONS, 2020, 11 (01)

[17] SIRPA is a specific cell-surface marker for isolating cardiomyocytes derived from human pluripotent stem cells [J].

Dubois, Nicole C. ;

Craft, April M. ;

Sharma, Parveen ;

Elliott, David A. ;

Stanley, Edouard G. ;

Elefanty, Andrew G. ;

Gramolini, Anthony ;

Keller, Gordon .

NATURE BIOTECHNOLOGY, 2011, 29 (11) :1011-U82

[18] Transcriptomic signatures across human tissues identify functional rare genetic variation [J].

Ferraro, Nicole M. ;

Strober, Benjamin J. ;

Einson, Jonah ;

Abell, Nathan S. ;

Aguet, Francois ;

Barbeira, Alvaro N. ;

Brandt, Margot ;

Bucan, Maja ;

Castel, Stephane E. ;

Davis, Joe R. ;

Greenwald, Emily ;

Hess, Gaelen T. ;

Hilliard, Austin T. ;

Kember, Rachel L. ;

Kotis, Bence ;

Park, YoSon ;

Peloso, Gina ;

Ramdas, Shweta ;

Scott, Alexandra J. ;

Smail, Craig ;

Tsang, Emily K. ;

Zekavat, Seyedeh M. ;

Ziosi, Marcello ;

Aradhana ;

Ardlie, Kristin G. ;

Assimes, Themistocles L. ;

Bassik, Michael C. ;

Brown, Christopher D. ;

Correa, Adolfo ;

Hall, Ira ;

Im, Hae Kyung ;

Li, Xin ;

Natarajan, Pradeep ;

Lappalainen, Tuuli ;

Mohammadi, Pejman ;

Montgomery, Stephen B. ;

Battlett, Alexis .

SCIENCE, 2020, 369 (6509) :1334-+

[19] COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer [J].

Forbes, Simon A. ;

Bindal, Nidhi ;

Bamford, Sally ;

Cole, Charlotte ;

Kok, Chai Yin ;

Beare, David ;

Jia, Mingming ;

Shepherd, Rebecca ;

Leung, Kenric ;

Menzies, Andrew ;

Teague, Jon W. ;

Campbell, Peter J. ;

Stratton, Michael R. ;

Futreal, P. Andrew .

NUCLEIC ACIDS RESEARCH, 2011, 39 :D945-D950

[20] Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts [J].

Fresard, Laure ;

Smail, Craig ;

Ferraro, Nicole M. ;

Teran, Nicole A. ;

Li, Xin ;

Smith, Kevin S. ;

Bonner, Devon ;

Kernohan, Kristin D. ;

Marwaha, Shruti ;

Zappala, Zachary ;

Balliu, Brunilda ;

Davis, Joe R. ;

Liu, Boxiang ;

Prybol, Cameron J. ;

Kohler, Jennefer N. ;

Zastrow, Diane B. ;

Reuter, Chloe M. ;

Fisk, Dianna G. ;

Grove, Megan E. ;

Davidson, Jean M. ;

Hartley, Taila ;

Joshi, Ruchi ;

Strober, Benjamin J. ;

Utiramerur, Sowmithri ;

Lind, Lars ;

Ingelsson, Erik ;

Battle, Alexis ;

Bejerano, Gill ;

Bernstein, Jonathan A. ;

Ashley, Euan A. ;

Boycott, Kym M. ;

Merker, Jason D. ;

Wheeler, Matthew T. ;

Montgomery, Stephen B. ;

Adams, David R. ;

Aday, Aaron ;

Alejandro, Mercedes E. ;

Allard, Patrick ;

Ashley, Euan A. ;

Azamian, Mahshid S. ;

Bacino, Carlos A. ;

Baker, Eva ;

Balasubramanyam, Ashok ;

Barseghyan, Hayk ;

Batzli, Gabriel F. ;

Beggs, Alan H. ;

Behnam, Babak ;

Bellen, Hugo J. ;

Bernstein, Jonathan A. ;

Berry, Gerard T. .

NATURE MEDICINE, 2019, 25 (06) :911-+

← 1 2 3 4 5 6 7 →