0000000000559774
AUTHOR
Peter Durda
Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging
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 ass…
Additional file 4 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging
Additional file 4. Assessment of genomic inflation and heterogeneity.
Duffy antigen receptor for chemokines (Darc) polymorphism regulates circulating concentrations of monocyte chemoattractant protein-1 and other inflammatory mediators
AbstractTo identify the genetic basis of circulating concentrations of monocyte chemoattractant protein-1 (MCP-1), we conducted genome-wide association analyses for MCP-1 in 3 independent cohorts (n = 9598). The strongest association was for serum MCP-1 with a nonsynonymous polymorphism, rs12075 (Asp42Gly) in DARC, the gene for Duffy antigen receptor for chemokines, a known vascular reservoir of proinflammatory cytokines (minor allele frequency, 45.6%; P < 1.0 * 10−323). This association was supported by family-based genetic linkage at a locus encompassing the DARC gene (genome-wide P = 8.0 * 10−13). Asp42Gly accounted for approximately 20% of the variability in serum MCP-1 concentration…
Additional file 3 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging
Additional file 3. Supplementary Figures - Figures S1-S31.
Additional file 6 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging
Additional file 6. Review history.
Additional file 5 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging
Additional file 5. Colocalization plots.
Additional file 1 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging
Additional file 1. Individual cohort descriptions and acknowledgements.
Additional file 5 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging
Additional file 5. Colocalization plots.
Additional file 6 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging
Additional file 6. Review history.
Genome-wide association studies identify 137 loci for DNA methylation biomarkers of ageing
AbstractBiological ageing estimators derived from DNA methylation (DNAm) data are heritable and correlate with morbidity and mortality. Leveraging DNAm and SNP data from >41,000 individuals, we identify 137 genome-wide significant loci (113 novel) from meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We report strong genetic correlations with longevity and lifestyle factors such as smoking, education, and obesity. Significant associations are observed in polygenic risk score analysis and to a lesser extent in Mendelian randomization analyses. This study illuminates the genetic …
Additional file 2 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging
Additional file 2. Supplementary Tables -Tables S1-S31.
Additional file 2 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging
Additional file 2. Supplementary Tables -Tables S1-S31.