Synchronized age-related gene expression changes across multiple tissues in human and the link to complex diseases

Yang, Jialiang; Huang, Tao; Petralia, Francesca; Long, Quan; Zhang, Bin; Argmann, Carmen; Zhao, Yong; Mobbs, Charles V.; Schadt, Eric; Zhu, Jun; Tu, Zhidong; GTEx Consortium; Monlong, Jean; Sammeth, Michael; Mele, Marta; Reverter, Ferran; Goldmann, Jakob; Guigó Serra, Roderic

Synchronized age-related gene expression changes across multiple tissues in human and the link to complex diseases

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dc.contributor.author Yang, Jialiangca
dc.contributor.author Huang, Taoca
dc.contributor.author Petralia, Francescaca
dc.contributor.author Long, Quanca
dc.contributor.author Zhang, Binca
dc.contributor.author Argmann, Carmenca
dc.contributor.author Zhao, Yongca
dc.contributor.author Mobbs, Charles V.ca
dc.contributor.author Schadt, Ericca
dc.contributor.author Zhu, Junca
dc.contributor.author Tu, Zhidongca
dc.contributor.author GTEx Consortiumca
dc.contributor.author Monlong, Jeanca
dc.contributor.author Sammeth, Michaelca
dc.contributor.author Mele, Martaca
dc.contributor.author Reverter, Ferranca
dc.contributor.author Goldmann, Jakobca
dc.contributor.author Guigó Serra, Rodericca
dc.date.accessioned 2016-04-27T13:46:44Z
dc.date.available 2016-04-27T13:46:44Z
dc.date.issued 2015
dc.description.abstract Aging is one of the most important biological processes and is a known risk factor for many age-related diseases in human. Studying age-related transcriptomic changes in tissues across the whole body can provide valuable information for a holistic understanding of this fundamental process. In this work, we catalogue age-related gene expression changes in nine tissues from nearly two hundred individuals collected by the Genotype-Tissue Expression (GTEx) project. In general, we find the aging gene expression signatures are very tissue specific. However, enrichment for some well-known aging components such as mitochondria biology is observed in many tissues. Different levels of cross-tissue synchronization of age-related gene expression changes are observed, and some essential tissues (e.g., heart and lung) show much stronger "co-aging" than other tissues based on a principal component analysis. The aging gene signatures and complex disease genes show a complex overlapping pattern and only in some cases, we see that they are significantly overlapped in the tissues affected by the corresponding diseases. In summary, our analyses provide novel insights to the co-regulation of age-related gene expression in multiple tissues; it also presents a tissue-specific view of the link between aging and age-related diseases.ca
dc.description.sponsorship JY is supported through Berg postdoc fellowship. ZT receives financial support from Berg Pharma as a consultant. ZT JZ ES receive support from Fondation Leducq Understanding coronary artery disease genes grant. The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health. Additional funds were provided by the NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. Donors were enrolled at Biospecimen Source Sites funded by NCI/SAIC-Frederick, Inc. (SAIC-F) subcontracts to the National Disease Research Interchange (10XS170), Roswell Park Cancer Institute (10XS171), and Science Care, Inc. (X10S172). The Laboratory, Data Analysis, and Coordinating Center (LDACC) was funded through a contract (HHSN268201000029C) to The Broad Institute, Inc. Biorepository operations were funded through an SAIC-F subcontract to Van Andel Institute (10ST1035). Additional data repository and project management were provided by SAIC-F (HHSN261200800001E). The Brain Bank was supported by supplements to University of Miami grants DA006227 & DA033684 and to contract N01MH000028. Statistical Methods development grants were made to the University of Geneva (MH090941 & MH101814), the University of Chicago (MH090951, MH090937, MH101820, MH101825), the University of North Carolina - Chapel Hill (MH090936 & MH101819), Harvard University (MH090948), Stanford University (MH101782), Washington University St Louis (MH101810), and the University of Pennsylvania (MH101822).
dc.format.mimetype application/pdfca
dc.identifier.citation Yang J, Huang T, Petralia F, Long Q, Zhang B, Argmann C et al. Synchronized age-related gene expression changes across multiple tissues in human and the link to complex diseases. Scientific reports. 2015;5:15145. DOI: 10.1038/srep15145ca
dc.identifier.doi http://dx.doi.org/10.1038/srep15145
dc.identifier.issn 2045-2322
dc.identifier.uri http://hdl.handle.net/10230/26189
dc.language.iso engca
dc.publisher Nature Publishing Groupca
dc.relation.ispartof Scientific reports. 2015;5:15145
dc.rights.accessRights info:eu-repo/semantics/openAccessca
dc.rights.uri http://creativecommons.org/licenses/by/4.0/ca
dc.subject.other Biologia computacionalca
dc.title Synchronized age-related gene expression changes across multiple tissues in human and the link to complex diseasesca
dc.type info:eu-repo/semantics/articleca
dc.type.version info:eu-repo/semantics/publishedVersionca

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