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Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

dc.contributor.authorMcCartney, Daniel L.
dc.contributor.authorMin, Josine L.
dc.contributor.authorRichmond, Rebecca C.
dc.contributor.authorLu, Ake T.
dc.contributor.authorSobczyk, Maria K.
dc.contributor.authorDavies, Gail
dc.contributor.authorBroer, Linda
dc.contributor.authorGuo, Xiuqing
dc.contributor.authorJeong, Ayoung
dc.contributor.authorJung, Jeesun
dc.contributor.authorKasela, Silva
dc.contributor.authorKatrinli, Seyma
dc.contributor.authorKuo, Pei-Lun
dc.contributor.authorMatias-Garcia, Pamela R.
dc.contributor.authorMishra, Pashupati P.
dc.contributor.authorNygaard, Marianne
dc.contributor.authorPalviainen, Teemu
dc.contributor.authorPatki, Amit
dc.contributor.authorRaffield, Laura M.
dc.contributor.authorRatliff, Scott M.
dc.contributor.authorRichardson, Tom G.
dc.contributor.authorRobinson, Oliver
dc.contributor.authorSoerensen, Mette
dc.contributor.authorSun, Dianjianyi
dc.contributor.authorTsai, Pei-Chien
dc.contributor.authorvan der Zee, Matthijs D.
dc.contributor.authorWalker, Rosie M.
dc.contributor.authorWang, Xiaochuan
dc.contributor.authorWang, Yunzhang
dc.contributor.authorXia, Rui
dc.contributor.authorXu, Zongli
dc.contributor.authorYao, Jie
dc.contributor.authorZhao, Wei
dc.contributor.authorCorrea, Adolfo
dc.contributor.authorBoerwinkle, Eric
dc.contributor.authorDugué, Pierre-Antoine
dc.contributor.authorDurda, Peter
dc.contributor.authorElliott, Hannah R.
dc.contributor.authorGieger, Christian
dc.contributor.authorThe Genetics of DNA Methylation Consortium
dc.contributor.authorde Geus, Eco J. C.
dc.contributor.authorHarris, Sarah E.
dc.contributor.authorHemani, Gibran
dc.contributor.authorImboden, Medea
dc.contributor.authorKähönen, Mika
dc.contributor.authorKardia, Sharon L. R.
dc.contributor.authorKresovich, Jacob K.
dc.contributor.authorLi, Shengxu
dc.contributor.authorLunetta, Kathryn L.
dc.contributor.authorMangino, Massimo
dc.contributor.authorMason, Dan
dc.contributor.authorMcIntosh, Andrew M.
dc.contributor.authorMengel-From, Jonas
dc.contributor.authorMoore, Ann Zenobia
dc.contributor.authorMurabito, Joanne M.
dc.contributor.authorNHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium
dc.contributor.authorOllikainen, Miina
dc.contributor.authorPankow, James S.
dc.contributor.authorPedersen, Nancy L.
dc.contributor.authorPeters, Annette
dc.contributor.authorPolidoro, Silvia
dc.contributor.authorPorteous, David J.
dc.contributor.authorRaitakari, Olli
dc.contributor.authorRich, Stephen S.
dc.contributor.authorSandler, Dale P.
dc.contributor.authorSillanpää, Elina
dc.contributor.authorSmith, Alicia K.
dc.contributor.authorSouthey, Melissa C.
dc.contributor.authorStrauch, Konstantin
dc.contributor.authorTiwari, Hemant
dc.contributor.authorTanaka, Toshiko
dc.contributor.authorTillin, Therese
dc.contributor.authorUitterlinden, Andre G.
dc.contributor.authorVan Den Berg, David J.
dc.contributor.authorvan Dongen, Jenny
dc.contributor.authorWilson, James G.
dc.contributor.authorWright, John
dc.contributor.authorYet, Idil
dc.contributor.authorArnett, Donna
dc.contributor.authorBandinelli, Stefania
dc.contributor.authorBell, Jordana T.
dc.contributor.authorBinder, Alexandra M.
dc.contributor.authorBoomsma, Dorret I.
dc.contributor.authorChen, Wei
dc.contributor.authorChristensen, Kaare
dc.contributor.authorConneely, Karen N.
dc.contributor.authorElliott, Paul
dc.contributor.authorFerrucci, Luigi
dc.contributor.authorFornage, Myriam
dc.contributor.authorHägg, Sara
dc.contributor.authorHayward, Caroline
dc.contributor.authorIrvin, Marguerite
dc.contributor.authorKaprio, Jaakko
dc.contributor.authorLawlor, Deborah A.
dc.contributor.authorLehtimäki, Terho
dc.contributor.authorLohoff, Falk W.
dc.contributor.authorMilani, Lili
dc.contributor.authorMilne, Roger L.
dc.contributor.authorProbst-Hensch, Nicole
dc.contributor.authorReiner, Alex P.
dc.contributor.authorRitz, Beate
dc.contributor.authorRotter, Jerome I.
dc.contributor.authorSmith, Jennifer A.
dc.contributor.authorTaylor, Jack A.
dc.contributor.authorvan Meurs, Joyce B. J.
dc.contributor.authorVineis, Paolo
dc.contributor.authorWaldenberger, Melanie
dc.contributor.authorDeary, Ian J.
dc.contributor.authorRelton, Caroline L.
dc.contributor.authorHorvath, Steve
dc.contributor.authorMarioni, Riccardo E.
dc.date.accessioned2021-07-08T05:21:53Z
dc.date.available2021-07-08T05:21:53Z
dc.date.issued2021
dc.identifier.citationMcCartney, D. L., Min, J. L., Richmond, R. C., Lu, A. T., Sobczyk, M. K., Davies, G., Broer, L., Guo, X., Jeong, A., Jung, J., Kasela, S., Katrinli, S., Kuo, P.-L., Matias-Garcia, P. R., Mishra, P. P., Nygaard, M., Palviainen, T., Patki, A., Raffield, L. M., . . . Marioni, R. E. (2021). Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging. <i>Genome Biology</i>, <i>22</i>, Article 194. <a href="https://doi.org/10.1186/s13059-021-02398-9" target="_blank">https://doi.org/10.1186/s13059-021-02398-9</a>
dc.identifier.otherCONVID_98927874
dc.identifier.urihttps://jyx.jyu.fi/handle/123456789/77041
dc.description.abstractBackground Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. Results Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. Conclusion This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.en
dc.format.mimetypeapplication/pdf
dc.language.isoeng
dc.publisherBiomed Central
dc.relation.ispartofseriesGenome Biology
dc.rightsCC BY 4.0
dc.subject.otherDNA methylation
dc.subject.otherGWAS
dc.subject.otherepigenetic clock
dc.titleGenome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging
dc.typearticle
dc.identifier.urnURN:NBN:fi:jyu-202107084227
dc.contributor.laitosLiikuntatieteellinen tiedekuntafi
dc.contributor.laitosFaculty of Sport and Health Sciencesen
dc.contributor.oppiaineGerontologia ja kansanterveysfi
dc.contributor.oppiaineGerontologian tutkimuskeskusfi
dc.contributor.oppiaineHyvinvoinnin tutkimuksen yhteisöfi
dc.contributor.oppiaineGerontology and Public Healthen
dc.contributor.oppiaineGerontology Research Centeren
dc.contributor.oppiaineSchool of Wellbeingen
dc.type.urihttp://purl.org/eprint/type/JournalArticle
dc.type.coarhttp://purl.org/coar/resource_type/c_2df8fbb1
dc.description.reviewstatuspeerReviewed
dc.relation.issn1474-7596
dc.relation.volume22
dc.type.versionpublishedVersion
dc.rights.copyright© The Author(s). 2021
dc.rights.accesslevelopenAccessfi
dc.subject.ysoepigenetiikka
dc.subject.ysogenomiikka
dc.subject.ysoDNA-metylaatio
dc.subject.ysoikääntyminen
dc.subject.ysobiomarkkerit
dc.format.contentfulltext
jyx.subject.urihttp://www.yso.fi/onto/yso/p24631
jyx.subject.urihttp://www.yso.fi/onto/yso/p5146
jyx.subject.urihttp://www.yso.fi/onto/yso/p38350
jyx.subject.urihttp://www.yso.fi/onto/yso/p5056
jyx.subject.urihttp://www.yso.fi/onto/yso/p12288
dc.rights.urlhttps://creativecommons.org/licenses/by/4.0/
dc.relation.doi10.1186/s13059-021-02398-9
dc.type.okmA1


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