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

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dc.contributor.author Genetics DNA Methylation Consort
dc.contributor.author NHLBI Trans-Omics Precision Med
dc.contributor.author McCartney, Daniel L.
dc.contributor.author Min, Josine L.
dc.contributor.author Richmond, Rebecca C.
dc.contributor.author Palviainen, Teemu
dc.contributor.author Ollikainen, Miina
dc.contributor.author Kaprio, Jaakko
dc.date.accessioned 2021-09-20T05:02:02Z
dc.date.available 2021-09-20T05:02:02Z
dc.date.issued 2021-06-29
dc.identifier.citation Genetics DNA Methylation Consort , NHLBI Trans-Omics Precision Med , McCartney , D L , Min , J L , Richmond , R C , Palviainen , T , Ollikainen , M & Kaprio , J 2021 , ' Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging ' , Genome Biology , vol. 22 , no. 1 , 194 . https://doi.org/10.1186/s13059-021-02398-9
dc.identifier.other PURE: 168605017
dc.identifier.other PURE UUID: 899d4acd-7e6c-4213-9254-7b7ece299c41
dc.identifier.other WOS: 000671146200002
dc.identifier.other ORCID: /0000-0003-3661-7400/work/100257124
dc.identifier.other ORCID: /0000-0002-7847-8384/work/100258168
dc.identifier.uri http://hdl.handle.net/10138/334448
dc.description.abstract Background 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.extent 25
dc.language.iso eng
dc.relation.ispartof Genome Biology
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject DNA methylation
dc.subject GWAS
dc.subject Epigenetic clock
dc.subject MENDELIAN RANDOMIZATION
dc.subject SUSCEPTIBILITY LOCI
dc.subject AGE
dc.subject METAANALYSIS
dc.subject ENRICHMENT
dc.subject REGRESSION
dc.subject INSIGHTS
dc.subject PROVIDES
dc.subject BLOOD
dc.subject 318 Medical biotechnology
dc.subject 11832 Microbiology and virology
dc.subject 1184 Genetics, developmental biology, physiology
dc.title Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging en
dc.type Article
dc.contributor.organization Institute for Molecular Medicine Finland
dc.contributor.organization Genetic Epidemiology
dc.contributor.organization Helsinki Institute of Life Science HiLIFE
dc.contributor.organization Department of Public Health
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1186/s13059-021-02398-9
dc.relation.issn 1474-760X
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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