Pre-diagnosis blood DNA methylation profiling of twin pairs discordant for breast cancer points to the importance of environmental risk DOI Creative Commons
Hannes Frederik Bode, Liang He, Jacob Hjelmborg

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 16, 2023

Abstract Background Assessment of breast cancer (BC) risk generally relies on mammography, family history, reproductive and genotyping major mutations. However, assessing the impact environmental factors, such as lifestyle, health related behavior or external exposures, is still challenging. DNA methylation (DNAm), capturing both genetic effects, presents a promising opportunity. Previous studies have identified associations predicted BC using DNAm in blood, however, these did not distinguish between contributions to sites. In this study, are assessed paired twin models, which control for shared allowing testing non-shared exposures behavior. Results Pre-diagnosis blood samples 32 monozygotic (MZ) 76 dizygotic (DZ) female pairs discordant were collected at mean age 56.0 years, with diagnosis 66.8 censoring 75.2 years. We 212 CpGs (p<6.4*10 −8 ) 15 DMRs associated across all Cox proportional hazard models. All but one hypomethylated 198/212 had their independent effects. According previous literature, least five top estrogen signaling. Following comprehensive two-sample Mendelian Randomization analysis, we found evidence supporting dual causal cg20145695 (gene body NXN , rs480351) increased estrogen-receptor positive decreased negative BC. Conclusion While effects rare, most appear be This suggests that could serve valuable biomarker factors BC, may offer potential benefits complementary tool current assessment procedures.

Language: Английский

Post-translational modifications of histone and non-histone proteins in epigenetic regulation and translational applications in alcohol-associated liver disease: Challenges and research opportunities DOI
Wiramon Rungratanawanich,

Jacob W. Ballway,

Xin Wang

et al.

Pharmacology & Therapeutics, Journal Year: 2023, Volume and Issue: 251, P. 108547 - 108547

Published: Oct. 13, 2023

Language: Английский

Citations

10
Early-life smoking, cardiovascular disease risk, and the mediating role of DNA methylation biomarkers of aging DOI Creative Commons

Chang Sheng,

Rui Zhou, Hongcai Wang

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 29, 2025

Early-life smoking is linked to biological aging and chronic diseases, yet its specific relationship with cardiovascular disease (CVD) risk the role of DNA methylation biomarkers as potential mediators that remain underexplored. In this study, we analyzed data from 2345 participants in National Health Nutrition Examination Survey (NHANES; 1999-2002). status was assessed on basis age initiation (ASI) categorized into three periods (SIPs): childhood (5-14 years), adolescence/adulthood (> 14 never smoked. (DNAm PhenoAge, DunedinPoAm, HorvathTelo) were measured, CVD outcomes determined via self-reported, physician-confirmed diagnoses. Multivariate logistic regression causal mediation analyses performed assess associations between SIP explore mediating effects those associations. Earlier more strongly associated an increased developing CVD, showing highest (OR = 1.95, 95% CI: 1.15-3.29; P 0.013). Furthermore, independently (1-year increase DNAm PhenoAge: OR 1.03, 1.01-1.05, < 0.001; 0.1-unit DunedinPoAm: 1.19, 1.00-1.40, 0.05; 1-kb HorvathTelo: 0.57, 0.34-0.96, 0.05). Subgroup analysis revealed association early-life stronger among individuals without household exposure (P for interaction 0.035). Moreover, compared status, later correlated delayed epigenetic aging, indicated by lower PhenoAge (β=-0.02, -0.03--0.01, 0.01), slower DunedinPoAm (β=-0.01, -0.01--0.01, 0.001), longer HorvathTelo (β 0.01, 0.01-0.01, 0.001). Mediation significantly mediated risk, accounting 6% total effect (ASI: ACME=-0.000100, 0.010; SIP: ACME 0.004796, 0.022). risk. partially mediates relationship, suggesting a target prevention. these findings highlight need early prevention reduce

Language: Английский

Citations

0
GABAergic mechanisms in alcohol dependence DOI
Mikko Uusi‐Oukari, Esa R. Korpi

International review of neurobiology, Journal Year: 2024, Volume and Issue: unknown, P. 75 - 123

Published: Jan. 1, 2024

Language: Английский

Citations

2
Pre-diagnosis blood DNA methylation profiling of twin pairs discordant for breast cancer points to the importance of environmental risk factors DOI Creative Commons
Hannes Frederik Bode, Liang He, Jacob Hjelmborg

et al.

Clinical Epigenetics, Journal Year: 2024, Volume and Issue: 16(1)

Published: Nov. 18, 2024

Abstract Background Assessment of breast cancer (BC) risk generally relies on mammography, family history, reproductive and genotyping major mutations. However, assessing the impact environmental factors, such as lifestyle, health-related behavior, or external exposures, is still challenging. DNA methylation (DNAm), capturing both genetic effects, presents a promising opportunity. Previous studies have identified associations predicted BC using DNAm in blood; however, these did not distinguish between contributions to sites. In this study, are assessed paired twin models, which control for shared allowing testing non-shared exposures behavior. Results Pre-diagnosis blood samples 32 monozygotic (MZ) 76 dizygotic (DZ) female pairs discordant were collected at mean age 56.0 years, with diagnosis 66.8 years censoring 75.2 years. We 212 CpGs ( p < 6.4*10 –8 ) 15 DMRs associated across all Cox proportional hazard models. All but one risks hypomethylated, 198/212 had their independent effects. According previous literature, least five top related estrogen signaling. Following comprehensive two-sample Mendelian randomization analysis, we found evidence supporting dual causal cg20145695 (gene body NXN , rs480351) increased receptor positive decreased negative BC. Conclusion While effects rare, most appear be This suggests that could serve valuable biomarker factors BC, may offer potential benefits complementary tool current assessment procedures.

Language: Английский

Citations

1
Two Clinically Implementable Digital PCR Assessments of DNA Methylation for Diagnosing Heavy Alcohol Consumption DOI Creative Commons
Robert A. Philibert, Steven R. H. Beach, Allan M. Andersen

et al.

Epigenomes, Journal Year: 2024, Volume and Issue: 9(1), P. 1 - 1

Published: Dec. 24, 2024

Heavy alcohol consumption (HAC) has a profound adverse effect on human health. Unfortunately, there is relative lack of tools that are easily implementable in clinical settings and can be used to supplement self-reporting the diagnosis management HAC. In part, this paucity due limitations currently available biological measures mismatch between needs clinicians managing We first review pros cons existing measures. Next, we underlying theory performance characteristics two recently developed methylation-sensitive digital PCR (MSdPCR) assays, referred as Alcohol T Score (ATS) ZSCAN25, for assessment chronic recent HAC, respectively. Finally, outline paradigm improving use disorders by utilizing these new markers consumption. conclude further studies understand test each epigenetic larger, diverse populations order.

Language: Английский

Citations

1
DNA methylation at DLGAP2 and risk for relapse in alcohol dependence during acamprosate treatment DOI Creative Commons

Fatih Özel,

Michela Di Criscio,

Diana Ioana Lupu

et al.

Drug and Alcohol Dependence, Journal Year: 2024, Volume and Issue: 256, P. 111116 - 111116

Published: Feb. 3, 2024

Alcohol use disorders are prevalent mental with significant health implications. Epigenetic alterations may play a role in their pathogenesis, as DNA methylation at several genes has been associated these disorders. We have previously shown that the DLGAP2 gene, coding for synaptic density protein, is alcohol dependence. In this study, we aimed to examine association between and treatment response among patients undergoing acamprosate treatment.

Language: Английский

Citations

0
Next‐generation biomarkers for alcohol consumption and alcohol use disorder diagnosis, prognosis, and treatment: A critical review DOI
Shaunna L. Clark, Emily E. Hartwell, Doo‐Sup Choi

et al.

Alcohol Clinical and Experimental Research, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 12, 2024

This critical review summarizes the current state of omics-based biomarkers in alcohol research field. We first provide definitions and background information on use disorder (AUD), biomarkers, "omic" technologies. next summarize using (1) genetic as risk/prognostic for onset alcohol-related problems progression from regular drinking to problematic (including AUD), (2) epigenetic diagnostic AUD risk consumption, (3) transcriptomic AUD, (4) metabolomic predictive response acamprosate subjects with AUD. In final section, clinical implications findings are discussed, recommendations made future research.

Language: Английский

Citations

0
Pre-diagnosis blood DNA methylation profiling of twin pairs discordant for breast cancer points to the importance of environmental risk DOI Creative Commons
Hannes Frederik Bode, Liang He, Jacob Hjelmborg

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 16, 2023

Abstract Background Assessment of breast cancer (BC) risk generally relies on mammography, family history, reproductive and genotyping major mutations. However, assessing the impact environmental factors, such as lifestyle, health related behavior or external exposures, is still challenging. DNA methylation (DNAm), capturing both genetic effects, presents a promising opportunity. Previous studies have identified associations predicted BC using DNAm in blood, however, these did not distinguish between contributions to sites. In this study, are assessed paired twin models, which control for shared allowing testing non-shared exposures behavior. Results Pre-diagnosis blood samples 32 monozygotic (MZ) 76 dizygotic (DZ) female pairs discordant were collected at mean age 56.0 years, with diagnosis 66.8 censoring 75.2 years. We 212 CpGs (p<6.4*10 −8 ) 15 DMRs associated across all Cox proportional hazard models. All but one hypomethylated 198/212 had their independent effects. According previous literature, least five top estrogen signaling. Following comprehensive two-sample Mendelian Randomization analysis, we found evidence supporting dual causal cg20145695 (gene body NXN , rs480351) increased estrogen-receptor positive decreased negative BC. Conclusion While effects rare, most appear be This suggests that could serve valuable biomarker factors BC, may offer potential benefits complementary tool current assessment procedures.

Language: Английский

Citations

0