6533b7cffe1ef96bd125859b
RESEARCH PRODUCT
Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging
Jacob K. KresovichJerome I. RotterJames S. PankowLaura M. RaffieldAndré G. UitterlindenHemant K. TiwariDorret I. BoomsmaDorret I. BoomsmaMarguerite R. IrvinKaare ChristensenKaare ChristensenLili MilaniJonas Mengel-fromJonas Mengel-fromScott M. RatliffPeter DurdaJames G. WilsonJames G. WilsonXiaochuan WangRui XiaJordana T. BellJenny Van DongenJenny Van DongenPamela R. Matias-garciaAlexander P. ReinerAndrew M. McintoshToshiko TanakaSharon L.r. KardiaRebecca C RichmondKonstantin StrauchKonstantin StrauchRosie M. WalkerDale P. SandlerAmit PatkiTeemu PalviainenWei ChenPei-chien TsaiPei-chien TsaiPei-chien TsaiMedea ImbodenMedea ImbodenStefania BandinelliMika KähönenXiuqing GuoStephen S. RichOliver RobinsonRiccardo E. MarioniJie YaoDebbie A LawlorPierre Antoine DuguéPierre Antoine DuguéPierre Antoine DuguéRoger L. MilneRoger L. MilneRoger L. MilneYunzhang WangJennifer A. SmithNancy L. PedersenMatthijs D. Van Der ZeeMatthijs D. Van Der ZeePashupati P. MishraPei-lun KuoSteve HorvathMiina OllikainenMassimo ManginoMassimo ManginoMelissa C. SoutheyMelissa C. SoutheyMelissa C. SoutheyAyoung JeongAyoung JeongLinda BroerDianjianyi SunTom G. RichardsonDavid Van Den BergJack A. TaylorBeate RitzJeesun JungCaroline L ReltonSarah E. HarrisJosine L. MinCaroline HaywardEric BoerwinkleJaakko KaprioMelanie WaldenbergerDavid J. PorteousSeyma KatrinliGibran HemaniOlli T. RaitakariOlli T. RaitakariPaolo VineisSilvia PolidoroKaren N. ConneelyChristian GiegerDonna K. ArnettMarianne NygaardMarianne NygaardMaria K. SobczykTherese TillinFalk W. LohoffAdolfo CorreaWei ZhaoElina SillanpääElina SillanpääZongli XuJoanne M. MurabitoJohn WrightGail DaviesSara HäggMette SoerensenMette SoerensenAlexandra M. BinderAnn Zenobia MooreEco J. C. De GeusEco J. C. De GeusTerho LehtimäkiDan MasonDaniel L. MccartneyMyriam FornageIan J. DearyAlicia K. SmithJoyce B. J. Van MeursAke T. LuHannah R ElliottAnnette PetersSilva KaselaIdil YetIdil YetLuigi FerrucciShengxu LiNicole Probst-henschNicole Probst-henschPaul ElliottKathryn L. Lunettasubject
AgingMultifactorial InheritanceBLOODEpigenetic clock05 Environmental SciencesbiomarkkeritGenome-wide association studyQH426-470Epigenesis Genetic/dk/atira/pure/core/keywords/icep0302 clinical medicineBiomarkers of agingGWASBiology (General)AdiposityGenetics11832 Microbiology and virology0303 health sciences318 Medical biotechnologyDNA methylation1184 Genetics developmental biology physiologygenomiikkaDna Methylation ; Epigenetic Clock ; Gwasddc:DNA-metylaatioINSIGHTSC-Reactive ProteinepigenetiikkaDNA methylationMENDELIAN RANDOMIZATION/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_beingEducational StatusICEPGenetic MarkersPROVIDESSUSCEPTIBILITY LOCIBioinformaticsQH301-705.5GenomicsBiology03 medical and health sciencesNHLBI Trans-Omics for Precision Medicine (TOPMed) ConsortiumAGESDG 3 - Good Health and Well-beingPlasminogen Activator Inhibitor 1REGRESSIONGeneticsHumansEpigeneticsGeneMETAANALYSIS030304 developmental biologyGenome HumanResearchGenetics of DNA Methylation Consortium06 Biological SciencesLipid MetabolismHuman geneticsGenetic architectureImmunity InnateikääntyminenGenetic LociCpG Islands08 Information and Computing Sciences3111 BiomedicineENRICHMENTepigenetic clock030217 neurology & neurosurgeryBiomarkersGenome-Wide Association StudyGranulocytesdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2021-06-29 |