0000000000559818
AUTHOR
Falk W. Lohoff
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.
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 …
Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs
AM Vicente - Cross-Disorder Group of the Psychiatric Genomics Consortium Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in …
Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways
G.B. and S.N. acknowledge funding support for this work from the National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. P.H.L. is supported by US National Institute of Mental Health (NIMH) grant K99MH101367. Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an an…
Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder
Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n ~ 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generat…
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.