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Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging.
- Source :
-
Genome biology [Genome Biol] 2021 Jun 29; Vol. 22 (1), pp. 194. Date of Electronic Publication: 2021 Jun 29. - Publication Year :
- 2021
-
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.<br />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.<br />Conclusion: This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.
- Subjects :
- Adiposity genetics
Adiposity immunology
Aging immunology
Biomarkers metabolism
C-Reactive Protein genetics
C-Reactive Protein immunology
CpG Islands
Educational Status
Genetic Markers
Genome, Human
Genome-Wide Association Study
Granulocytes cytology
Granulocytes immunology
Humans
Immunity, Innate
Lipid Metabolism genetics
Lipid Metabolism immunology
Plasminogen Activator Inhibitor 1 genetics
Plasminogen Activator Inhibitor 1 immunology
Aging genetics
DNA Methylation
Epigenesis, Genetic
Genetic Loci
Multifactorial Inheritance
Subjects
Details
- Language :
- English
- ISSN :
- 1474-760X
- Volume :
- 22
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Genome biology
- Publication Type :
- Academic Journal
- Accession number :
- 34187551
- Full Text :
- https://doi.org/10.1186/s13059-021-02398-9