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McCartney, 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.* ; Ratliff, S.M.* ; Richardson, T.G.* ; Robinson, O.* ; Soerensen, M.* ; Sun, D.* ; Tsai, P.C.* ; van der Zee, M.D.* ; Walker, R.M.* ; Wang, X.* ; Wang, Y.* ; Xia, R.* ; Xu, Z.* ; Yao, J.* ; Zhao, W.* ; Correa, A.* ; Boerwinkle, E.* ; Dugué, P.A.* ; Durda, P.* ; Elliott, H.R.* ; Gieger, C. ; de Geus, E.J.C.* ; Harris, S.E.* ; Hemani, G.* ; Imboden, M.* ; Kähönen, M.* ; Kardia, S.L.R.* ; Kresovich, J.K.* ; Li, S.* ; Lunetta, K.L.* ; Mangino, M.* ; Mason, D.* ; McIntosh, A.M.* ; Mengel-From, J.* ; Moore, A.Z.* ; Murabito, J.M.* ; Ollikainen, M.* ; Pankow, J.S.* ; Pedersen, N.L.* ; Peters, A. ; Polidoro, S.* ; Porteous, D.J.* ; Raitakari, O.* ; Rich, S.S.* ; Sandler, D.P.* ; Sillanpää, E.* ; Smith, A.K.* ; Southey, M.C.* ; Strauch, K. ; Tiwari, H.* ; Tanaka, T.* ; Tillin, T.* ; Uitterlinden, A.G.* ; Van Den Berg, D.J.* ; van Dongen, J.* ; Wilson, J.G.* ; Wright, J.* ; Yet, I.* ; Arnett, D.* ; Bandinelli, S.* ; Bell, J.T.* ; Binder, A.M.* ; Boomsma, D.I.* ; Chen, W.* ; Christensen, K.* ; Conneely, K.N.* ; Elliott, P.* ; Ferrucci, L.* ; Fornage, M.* ; Hägg, S.* ; Hayward, C.* ; Irvin, M.R.* ; Kaprio, J.* ; Lawlor, D.A.* ; Lehtimäki, T.* ; Lohoff, F.W.* ; Milani, L.* ; Milne, R.L.* ; Probst-Hensch, N.* ; Reiner, A.P.* ; Ritz, B.* ; Rotter, J.I.* ; Smith, J.A.* ; Taylor, J.A.* ; van Meurs, J.B.J.* ; Vineis, P.* ; Waldenberger, M. ; Deary, I.J.* ; Relton, C.L.* ; Horvath, S.* ; Marioni, R.E.*

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

Genome Biol. 22:194 (2021)
Postprint Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Dna Methylation ; Epigenetic Clock ; Gwas; Mendelian Randomization; Susceptibility Loci; Age; Metaanalysis; Gwas; Enrichment; Regression; Insights; Provides; Blood
ISSN (print) / ISBN 1474-760X
e-ISSN 1465-6906
Zeitschrift Genome Biology
Quellenangaben Band: 22, Heft: 1, Seiten: , Artikelnummer: 194 Supplement: ,
Verlag BioMed Central
Verlagsort Campus, 4 Crinan St, London N1 9xw, England
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology II (EPI2)
Institute of Genetic Epidemiology (IGE)
Förderungen Medical Research Council
Cancer Research UK
Alzheimer's Research UK
NIH HHS