0000000000559823

AUTHOR

Beate Ritz

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…

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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.

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Impact of Parkinson's disease risk loci on age at onset

Background The aim of this study was to assess whether recently identified Parkinson's disease (PD) risk genes also influence age at onset in PD. Methods We genotyped 23 single-nucleotide polymorphisms in 1,526 Danish PD patients and performed linear regression analyses with age at onset. The combined impact of PD risk loci on age at onset was assessed by linear regression analyses using a weighted genetic risk score. Results The strongest effects were observed with rs12726330 in GBA (beta = –3.63, P = 2.0 × 10−5) and rs34311866 in TMEM175/GAK (beta = –1.19, P = 4.0 × 10−3), corresponding to a 3.6-y and 1.2-y decrease of age at onset per risk allele, respectively. The weighted genetic risk …

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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.

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Additional file 6 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Additional file 6. Review history.

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Additional file 5 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Additional file 5. Colocalization plots.

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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.

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Additional file 5 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Additional file 5. Colocalization plots.

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Additional file 6 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Additional file 6. Review history.

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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 …

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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.

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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.

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