Genome-wide DNA methylation analysis of peripheral blood samples of psychiatric patients and healthy controls
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE222468 | GEO | 2023/01/14
REPOSITORIES: GEO
Similar Datasets
Project description:We evaluated biological aging using two epigenetic clocks (Horvath’s multi-tissue clock and CorticalClock (Shireby et al.)Brain 2020) calculated from DNA methylation measured in human post-mortem brain (orbitofrontal cortex; BA11) in a trans-diagnostic psychiatric sample including healthy controls. Epigenome-wide DNA methylation profiling was performed with the Illumina Infinium MethylationEPIC BeadChip (version 1.0; Illumina, San Diego, CA, USA) according to manufacturer’s guidelines. The total cohort consisted of 91 individuals. Five individuals were run in duplicate (as internal control). Individuals were either diagnosed a psychiatric disease (1) or psychiatrically healthy (0). Independent of the epigenetic clock used, we did not find evidence for accelerated epigenetic aging in individuals diagnosed with a psychiatric disorder.
2024-07-17 | GSE254293 | GEO
Project description:We assessed DNA methylation in whole blood samples from an Australian population across different age groups. Our study focused on evaluating the accuracy of DNA methylation age estimation using the Horvath 2018 and PhenoAge clocks. Additionally, we examined previously reported functional measures of aging in peripheral blood mononuclear cells (PBMCs). Our findings indicated that DNA methylation age effectively predicted donor age, while only a limited number of tested cell functions showed correlations with donor age.
2023-09-15 | GSE235717 | GEO
Project description:Background: Increased epigenetic age acceleration (EAA) in survivors of childhood cancer is associated with specific treatment exposures, unfavorable health behaviors, and presence of certain chronic health conditions. To better understand inter-individual variability, we investigated the genetic basis underlying EAA. Methods: Genome-wide association studies of EAA based on multiple epigenetic clocks (Hannum, Horvath, PhenoAge, and GrimAge) were performed. MethylationEPIC BeadChip array and whole-genome sequencing data were generated with blood-derived DNA from participants in the St. Jude Lifetime Cohort Study (discovery: 2,138 pre-existing and 502 newly generated data, all survivors; exploratory: 282 community controls). Linear regression models were fit for each epigenetic age against allelic dose of each genetic variant, adjusting for age at sampling, sex, and cancer treatment exposures. Fixed-effects meta-analysis was used to combine summary statistics from two discovery data sets. LD (Linkage disequilibrium) score regression was used to estimate single-nucleotide polymorphism (SNP)-based heritability. Results: For EAA-Horvath, a genome-wide significant association was mapped to SELP gene with the strongest SNP rs732314 (meta-GWAS: β=0.57, P=3.30×10-11). Moreover, the stratified analysis of the association between rs732314 and EAA-Horvath showed substantial heterogeneity between children and adults (meta-GWAS: β=0.97 vs. 0.51, I2=73.1%) as well as between survivors with and without chest/abdominal/pelvic-RT exposure (β=0.64 vs. 0.31, I2=66.3%). For EAA-Hannum, an association was mapped to HLA locus with the strongest SNP rs28366133 (meta-GWAS: β=0.78, P=3.78×10-11). There was no genome-wide significant hit for EAA-PhenoAge or EAA-GrimAge. Interestingly, among community controls, rs732314 was associated with EAA-Horvath (β=1.09, P=5.43×10-5), whereas rs28366133 was not associated with EAA-Hannum (β=0.21, P=0.49). The estimated heritability was 0.33 (SE=0.20) for EAA-Horvath and 0.17 (SE=0.23) for EAA-Hannum, but close to zero for EAA-PhenoAge and EAA-GrimAge. Conclusions: We identified novel genetic variants in SELP gene and HLA region associated with EAA-Horvath and EAA-Hannum, respectively, among survivors of childhood cancer. The new genetic variants in combination with other replicated known variants can facilitate identification of survivors at higher risk in developing accelerated aging, and potentially inform drug targets for future intervention strategies among vulnerable survivors.
2022-03-09 | GSE197674 | GEO
Project description:Background: Increased epigenetic age acceleration (EAA) in survivors of childhood cancer is associated with specific treatment exposures, unfavorable health behaviors, and presence of certain chronic health conditions. To better understand inter-individual variability, we investigated the genetic basis underlying EAA. Methods: Genome-wide association studies of EAA based on multiple epigenetic clocks (Hannum, Horvath, PhenoAge, and GrimAge) were performed. MethylationEPIC BeadChip array and whole-genome sequencing data were generated with blood-derived DNA from participants in the St. Jude Lifetime Cohort Study (discovery: 2,138 pre-existing and 502 newly generated data, all survivors; exploratory: 282 community controls). Linear regression models were fit for each epigenetic age against allelic dose of each genetic variant, adjusting for age at sampling, sex, and cancer treatment exposures. Fixed-effects meta-analysis was used to combine summary statistics from two discovery data sets. LD (Linkage disequilibrium) score regression was used to estimate single-nucleotide polymorphism (SNP)-based heritability. Results: For EAA-Horvath, a genome-wide significant association was mapped to SELP gene with the strongest SNP rs732314 (meta-GWAS: β=0.57, P=3.30×10-11). Moreover, the stratified analysis of the association between rs732314 and EAA-Horvath showed substantial heterogeneity between children and adults (meta-GWAS: β=0.97 vs. 0.51, I2=73.1%) as well as between survivors with and without chest/abdominal/pelvic-RT exposure (β=0.64 vs. 0.31, I2=66.3%). For EAA-Hannum, an association was mapped to HLA locus with the strongest SNP rs28366133 (meta-GWAS: β=0.78, P=3.78×10-11). There was no genome-wide significant hit for EAA-PhenoAge or EAA-GrimAge. Interestingly, among community controls, rs732314 was associated with EAA-Horvath (β=1.09, P=5.43×10-5), whereas rs28366133 was not associated with EAA-Hannum (β=0.21, P=0.49). The estimated heritability was 0.33 (SE=0.20) for EAA-Horvath and 0.17 (SE=0.23) for EAA-Hannum, but close to zero for EAA-PhenoAge and EAA-GrimAge. Conclusions: We identified novel genetic variants in SELP gene and HLA region associated with EAA-Horvath and EAA-Hannum, respectively, among survivors of childhood cancer. The new genetic variants in combination with other replicated known variants can facilitate identification of survivors at higher risk in developing accelerated aging, and potentially inform drug targets for future intervention strategies among vulnerable survivors.
2022-03-09 | GSE197675 | GEO
Project description:Background: Increased epigenetic age acceleration (EAA) in survivors of childhood cancer is associated with specific treatment exposures, unfavorable health behaviors, and presence of certain chronic health conditions. To better understand inter-individual variability, we investigated the genetic basis underlying EAA. Methods: Genome-wide association studies of EAA based on multiple epigenetic clocks (Hannum, Horvath, PhenoAge, and GrimAge) were performed. MethylationEPIC BeadChip array and whole-genome sequencing data were generated with blood-derived DNA from participants in the St. Jude Lifetime Cohort Study (discovery: 2,138 pre-existing and 502 newly generated data, all survivors; exploratory: 282 community controls). Linear regression models were fit for each epigenetic age against allelic dose of each genetic variant, adjusting for age at sampling, sex, and cancer treatment exposures. Fixed-effects meta-analysis was used to combine summary statistics from two discovery data sets. LD (Linkage disequilibrium) score regression was used to estimate single-nucleotide polymorphism (SNP)-based heritability. Results: For EAA-Horvath, a genome-wide significant association was mapped to SELP gene with the strongest SNP rs732314 (meta-GWAS: β=0.57, P=3.30×10-11). Moreover, the stratified analysis of the association between rs732314 and EAA-Horvath showed substantial heterogeneity between children and adults (meta-GWAS: β=0.97 vs. 0.51, I2=73.1%) as well as between survivors with and without chest/abdominal/pelvic-RT exposure (β=0.64 vs. 0.31, I2=66.3%). For EAA-Hannum, an association was mapped to HLA locus with the strongest SNP rs28366133 (meta-GWAS: β=0.78, P=3.78×10-11). There was no genome-wide significant hit for EAA-PhenoAge or EAA-GrimAge. Interestingly, among community controls, rs732314 was associated with EAA-Horvath (β=1.09, P=5.43×10-5), whereas rs28366133 was not associated with EAA-Hannum (β=0.21, P=0.49). The estimated heritability was 0.33 (SE=0.20) for EAA-Horvath and 0.17 (SE=0.23) for EAA-Hannum, but close to zero for EAA-PhenoAge and EAA-GrimAge. Conclusions: We identified novel genetic variants in SELP gene and HLA region associated with EAA-Horvath and EAA-Hannum, respectively, among survivors of childhood cancer. The new genetic variants in combination with other replicated known variants can facilitate identification of survivors at higher risk in developing accelerated aging, and potentially inform drug targets for future intervention strategies among vulnerable survivors.
2022-03-09 | GSE197676 | GEO
Project description:Opioid abuse poses significant risk to individuals in the United States and epigenetic changes are a leading potential biomarker of opioid abuse. Current evidence, however, is mostly limited to candidate gene analysis in whole blood. Here, we provide Illumina HumanMethylationEPIC array data generated in dorsolateral prefrontal cortex tissue from 153 deceased invidiuals: 72 who died of acute opioid intoxication, 53 psychiatric controls, and 28 normal controls. Using these data, we conducted an epigenome-wide association study and identified one CpG site within a gene (NTN1) that may be related to opioid use. We also detected accelerated PhenoAge in opioid samples compared to control samples.
2021-04-01 | GSE164822 | GEO
Project description:Anorexia nervosa (AN), bulimia nervosa (BN), and obsessive-compulsive disorder (OCD) are complex psychiatric disorders with shared obsessive features, thought to arise from the interaction of multiple genes of small effect with environmental factors. Potential candidate genes for AN, BN, and OCD have been identified through clinical association and neuroimaging studies; however, recent genome-wide association studies of eating disorders (ED) so far have failed to report significant findings. Additionally, few if any studies have interrogated postmortem brain tissue for evidence of eQTLs associated with candidate genes, which has particular promise as an approach to elucidating molecular mechanisms of association. We therefore selected single nucleotide polymorphisms (SNPs) based on candidate gene studies for AN, BN, and OCD from the literature, and examined the association of these SNPs with gene expression across the lifespan in prefrontal cortex of a non-psychiatric control cohort (N=268). Several risk-predisposing SNPs were significantly associated with gene expression among control subjects. We then measured gene expression in the prefrontal cortex of cases previously diagnosed with obsessive psychiatric disorders, e.g., eating disorders (ED; N=15), and obsessive-compulsive disorder/obsessive-compulsive personality disorder or tics (OCD/OCPD/Tic; N=16), and non-psychiatric controls (N=102) and identified 6 and 286 genes that were differentially expressed between ED compared to controls and OCD cases compared to controls, respectively (FDR < 5%). However, none of the clinical risk SNPs were among the eQTLs and none were significantly associated with gene expression within the broad obsessive cohort, suggesting larger sample sizes or other brain regions may be required to identify candidate molecular mechanisms of clinical association in postmortem brain datasets. Gene expression data from the dorsolateral prefrontal cortex (DLPFC) from postmortem tissue on 133 subjects - 15 eating disorder (ED) patients, 16 obessive compulsive disorder (OCD) patients, and 102 non-psychiatric controls - run on the Illumina HumanHT-12 v3 microarray
2014-08-08 | E-GEOD-60190 | biostudies-arrayexpress
Project description:Transient reprogramming, mediated by transient expression of mRNAs, promotes a rapid reversal of both cellular aging and of epigenetic clock in human fibroblasts and endothelial cells. Transient on-integrative reprogramming protocol optimized based on a cocktail of mRNAs expressing OCT4, SOX2, KLF4, c-MYC, LIN28 and NANOG (OSKMLN). This protocol consistently produces induced pluripotent stem cell (iPSC) colonies, regardless of age of the donors, after 12-15 daily transfections. Here we adopted a transient reprogramming protocol where OSKMLN were daily transfected for only four consecutive days. Methylation profiles were used to estimate two epigenetic clocks: the pan tissue clock from Horvath 2013 (PubMedIdentifier PMID: 24138928 or PMCID: PMC4015143) and the skin & blood clock from Horvath 2018 (PMID: 30048243 PMCID: PMC6075434).
2020-01-21 | GSE142439 | GEO
Project description:Epigenetic clocks are age predictors that use machine-learning models trained on DNA CpG methylation values to predict chronological or biological age. Increases in predicted epigenetic age relative to chronological age (epigenetic age acceleration) are connected to aging-associated pathologies, and changes in epigenetic age are linked to canonical aging hallmarks. However, epigenetic clocks rely on training data from bulk tissues whose cellular composition changes with age. We found that human naive CD8+ T cells, which decrease during aging, exhibit an epigenetic age 15–20 years younger than effector memory CD8+ T cells from the same individual. Importantly, homogenous naive T cells isolated from individuals of different ages show a progressive increase in epigenetic age, indicating that current epigenetic clocks measure two independent variables, aging and immune cell composition. To isolate the age-associated cell intrinsic changes, we created a new clock, the IntrinClock, that did not change among 10 immune cell types tested. IntrinClock showed a robust predicted epigenetic age increase in a model of replicative senescence in vitro and age reversal during OSKM-mediated reprogramming
2023-12-27 | GSE252045 | GEO
Project description:Anorexia nervosa (AN), bulimia nervosa (BN), and obsessive-compulsive disorder (OCD) are complex psychiatric disorders with shared obsessive features, thought to arise from the interaction of multiple genes of small effect with environmental factors. Potential candidate genes for AN, BN, and OCD have been identified through clinical association and neuroimaging studies; however, recent genome-wide association studies of eating disorders (ED) so far have failed to report significant findings. Additionally, few if any studies have interrogated postmortem brain tissue for evidence of eQTLs associated with candidate genes, which has particular promise as an approach to elucidating molecular mechanisms of association. We therefore selected single nucleotide polymorphisms (SNPs) based on candidate gene studies for AN, BN, and OCD from the literature, and examined the association of these SNPs with gene expression across the lifespan in prefrontal cortex of a non-psychiatric control cohort (N=268). Several risk-predisposing SNPs were significantly associated with gene expression among control subjects. We then measured gene expression in the prefrontal cortex of cases previously diagnosed with obsessive psychiatric disorders, e.g., eating disorders (ED; N=15), and obsessive-compulsive disorder/obsessive-compulsive personality disorder or tics (OCD/OCPD/Tic; N=16), and non-psychiatric controls (N=102) and identified 6 and 286 genes that were differentially expressed between ED compared to controls and OCD cases compared to controls, respectively (FDR < 5%). However, none of the clinical risk SNPs were among the eQTLs and none were significantly associated with gene expression within the broad obsessive cohort, suggesting larger sample sizes or other brain regions may be required to identify candidate molecular mechanisms of clinical association in postmortem brain datasets.
2014-08-08 | GSE60190 | GEO