|Title||Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging.|
|Publication Type||Journal Article|
|Year of Publication||2021|
|Authors||McCartney DL, Min JL, Richmond RC, et al.|
|Corporate Authors||Genetics of DNA Methylation Consortium, NHLBI Trans-Omics for Precision Medicine(TOPMed) Consortium|
|Date Published||2021 06 29|
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.
|Alternate Journal||Genome Biol|
|PubMed Central ID||PMC8243879|
|Grant List||MC_UU_00011/5 / MRC_ / Medical Research Council / United Kingdom |
C18281/A191169 / CRUK_ / Cancer Research UK / United Kingdom
R01 HL133221 / HL / NHLBI NIH HHS / United States
MR/R0245065/1 / MRC_ / Medical Research Council / United Kingdom
U01 AG060908 / AG / NIA NIH HHS / United States
R01 HL120393 / HL / NHLBI NIH HHS / United States
U01 HL120393 / HL / NHLBI NIH HHS / United States
HHSN268201000001I / HL / NHLBI NIH HHS / United States
HHSN268201000021C / HL / NHLBI NIH HHS / United States
R01 HL117626 / HL / NHLBI NIH HHS / United States
R01 AG054628 / AG / NIA NIH HHS / United States