Journal
GENOME BIOLOGY
Volume 22, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s13059-021-02398-9
Keywords
DNA methylation; GWAS; Epigenetic clock
Funding
- National Institute of Health [U01AG060908-01, 1R01AG054628-01A1]
- Alzheimer's Research UK [ARUK-PG2017B-10]
- Cancer Research UK Program Grant [C18281/A191169]
- UK Medical Research Council Integrative Epidemiology Unit at the University of Bristol [MC_UU_00011/5]
- Age UK (Disconnected Mind program), UKRI Medical Research Council [MR/R0245065/1]
- University of Edinburgh School of Philosophy, Psychology and Language Sciences
- National Heart, Lung and Blood Institute (NHLBI)
- TOPMed Informatics Research Center [3R01HL-117626-02S1, HHSN268201800002I, R01HL-120393, U01HL120393, HHSN268201800001I]
- MRC [MC_UU_00011/5] Funding Source: UKRI
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This study identified 137 genome-wide significant loci, of which 113 are novel, related to epigenetic aging using DNA methylation and SNP data from over 40,000 individuals. The findings illuminate the genetic architecture underlying epigenetic aging, including shared genetic contributions with lifestyle factors and longevity.
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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