0000000000066601

AUTHOR

Silvia Polidoro

0000-0003-2968-0575

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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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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Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption

Alcohol consumption is a moderately heritable trait, but the genetic basis in humans is largely unknown, despite its clinical and societal importance. We report a genome-wide association study meta-analysis of ∼2.5 million directly genotyped or imputed SNPs with alcohol consumption (gram per day per kilogram body weight) among 12 population-based samples of European ancestry, comprising 26,316 individuals, with replication genotyping in an additional 21,185 individuals. SNP rs6943555 in autism susceptibility candidate 2 gene ( AUTS2 ) was associated with alcohol consumption at genome-wide significance ( P = 4 × 10 −8 to P = 4 × 10 −9 ). We found a genotype-specific expression of AUTS2 in 9…

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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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