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

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Genetics DNA Methylation Consort , NHLBI Trans-Omics Precision Med , McCartney , D L , Min , J L , Richmond , R C , Palviainen , T , Ollikainen , M & Kaprio , J 2021 , ' Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging ' , Genome Biology , vol. 22 , no. 1 , 194 . https://doi.org/10.1186/s13059-021-02398-9

Title: Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging
Author: Genetics DNA Methylation Consort; NHLBI Trans-Omics Precision Med; McCartney, Daniel L.; Min, Josine L.; Richmond, Rebecca C.; Palviainen, Teemu; Ollikainen, Miina; Kaprio, Jaakko
Contributor: University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
Date: 2021-06-29
Language: eng
Number of pages: 25
Belongs to series: Genome Biology
ISSN: 1474-760X
URI: http://hdl.handle.net/10138/334448
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.
Subject: DNA methylation
GWAS
Epigenetic clock
MENDELIAN RANDOMIZATION
SUSCEPTIBILITY LOCI
AGE
METAANALYSIS
ENRICHMENT
REGRESSION
INSIGHTS
PROVIDES
BLOOD
318 Medical biotechnology
11832 Microbiology and virology
1184 Genetics, developmental biology, physiology
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