Epigenetic scores indicate differences in the proteome of preterm infants DOI Creative Commons
K. I. M. McKinnon, Eleanor L.S. Conole, Kadi Vaher

et al.

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

Published: Dec. 19, 2023

Abstract Background Epigenetic scores (EpiScores), reflecting DNA methylation (DNAm)-based surrogates for complex traits, have been developed multiple circulating proteins. EpiScores pro-inflammatory proteins, such as C-reactive protein (DNAm CRP), are associated with brain health and cognition in adults inflammatory comorbidities of preterm birth neonates. Social disadvantage can become embedded child development through inflammation, deprivation is over-represented infants. We tested the hypotheses that socioeconomic status (SES) alterations a set enriched inflammation-associated Results 104 were derived from saliva samples 332 neonates born at gestational age (GA) 22.14 to 42.14 weeks. Saliva sampling was between 36.57 47.14 Forty-three (41%) low GA (standardised estimates |0.14 0.88|, Bonferroni-adjusted p -value <8.3×10 −3 ). These included chemokines, growth factors, proteins involved neurogenesis vascular development, cell membrane receptors, other immune Three SES, or interaction SES: afamin, intercellular adhesion molecule 5 hepatocyte factor-like |0.06 0.13|, In sub-group (n=217, median [range] 29.29 weeks [22.14 33.0 weeks]), SES-EpiScore associations did not remain statistically significant after adjustment sepsis, bronchopulmonary dysplasia, necrotising enterocolitis, histological chorioamnionitis. Conclusions Low substantially EpiScores. The providing new insights into dysregulation SES had fewer EpiScores; these tended small effect sizes adjusting comorbidities. This suggests inflammation unlikely be primary axis which becomes infants neonatal period.

Language: Английский

Blood-based epigenome-wide analyses of chronic low-grade inflammation across diverse population cohorts DOI Creative Commons
Robert F. Hillary,

Hong Kiat Ng,

Daniel L. McCartney

et al.

Cell Genomics, Journal Year: 2024, Volume and Issue: 4(5), P. 100544 - 100544

Published: April 30, 2024

Highlights•Existing DNAm predictors explain 10% of variance in circulating CRP levels•An elastic-net-based predictor outperforms existing models and explains 20% variance•Newly described is consistent across life course ancestries•This methods health outcome associationsSummaryChronic inflammation a hallmark age-related disease states. The effectiveness inflammatory proteins including C-reactive protein (CRP) assessing long-term hindered by their phasic nature. DNA methylation (DNAm) signatures may act as more reliable markers chronic inflammation. We show that inter-individual differences capture 50% the (N = 17,936, Generation Scotland). develop series using state-of-the-art algorithms. An elastic-net-regression-based outperformed competing explained 18% phenotypic Lothian Birth Cohort 1936 (LBC1936) cohort, doubling predictors. performed comparably four additional test cohorts (Avon Longitudinal Study Parents Children, Health for Life Singapore, Southall Brent Revisited, LBC1921), individuals diverse genetic ancestry different age groups. best-performing surpassed assay-measured score its associations with 26 outcomes. Our findings forge new avenues low-grade populations.Graphical abstract

Language: Английский

Citations

12
The association between maternal immune activation and brain structure and function in human offspring: a systematic review DOI
Anna Suleri, Anna‐Sophie Rommel, Olga Dmitrichenko

et al.

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 28, 2024

Language: Английский

Citations

6
Telehealth Parenting Program and Salivary Epigenetic Biomarkers in Preschool Children With Developmental Delay DOI Creative Commons
Sarah M. Merrill, Christina M. Hogan, Anne K. Bozack

et al.

JAMA Network Open, Journal Year: 2024, Volume and Issue: 7(7), P. e2424815 - e2424815

Published: July 29, 2024

Children with developmental delays are at a heightened risk of experiencing mental health challenges, and this is exacerbated among racially minoritized children who face disproportionate adversity. Understanding the impact parenting interventions on biological markers associated these risks crucial for mitigating long-term disparities. To examine effect 20 weeks an internet-based parent-child interaction training (iPCIT) program biomarkers aging chronic inflammation preschoolers delay 12-month follow-up. An observational secondary analysis data from randomized clinical trial conducted March 17, 2016, to December 15, 2020, assess changes in salivary DNA methylation (DNAm)-derived following iPCIT intervention. Participants were recruited 3 Part C early intervention sites large southeastern US city. Eligible participants included within months their third birthday had Child Behavior Checklist Externalizing Problems T score greater than 60 provided saliva least 1 study wave. Data was May 2023 April 2024. received either (a telehealth therapeutic focused enhancing relationship addressing behavioral challenges young children) or referrals as usual. DNAm follow-up assessed using Infinium HumanMethylationEPIC Bead Chip Assay derive DunedinPACE, C-reactive protein (CRP), interleukin-6 (IL-6). Analyses intent-to-treat used path analysis. A total 71 (mean [SD] age, 36.27 [0.61] 51 male [71.8%] female [28.2%]) analyzed, whom 34 37 The group slower pace (β = 0.26; 95% CI, 0.06 0.50; P .03) less DNAm-derived CRP 0.27; 0.05 0.49; .01) relative control condition These associations remained significant after accounting baseline score, child demographics, symptom severity, independent predicted buccal epithelial cell proportion both DunedinPACE CRP. There no association IL-6 0.14; -0.08 0.36; .21). In intervention, iPCIT, decreased molecular suggests potential modify aspects embedding stress. systemic such offers insights into disparities promoting resilience vulnerable populations. ClinicalTrials.gov Identifier: NCT03260816.

Language: Английский

Citations

5
Epigenetic scores of blood-based proteins as biomarkers of general cognitive function and brain health DOI Creative Commons
Hannah M. Smith, Joanna E. Moodie, Karla Monterrubio‐Gómez

et al.

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

Published: March 25, 2024

Abstract Background Epigenetic Scores (EpiScores) for blood protein levels have been associated with disease outcomes and measures of brain health, highlighting their potential usefulness as clinical biomarkers. They are typically derived via penalised regression, whereby a linear weighted sum DNA methylation (DNAm) at CpG sites predictive levels. Here, we examine 84 previously published EpiScores possible biomarkers cross-sectional longitudinal general cognitive function incident dementia across three independent cohorts. Results Using candidate biomarkers, associations (both cross-sectionally longitudinally) were tested in cohorts: Generation Scotland (GS), the Lothian Birth Cohorts 1921 1936 (LBC1921 LBC1936, respectively). A meta-analysis functioning results all cohorts identified 18 EpiScore (absolute meta-analytic standardised estimates ranged from 0.03 to 0.14, median 0.04, P FDR < 0.05). Several also observed between global volumetric LBC1936. An S100A9 (a known Alzheimer biomarker) was (meta-analytic beta: − 0.06, = 1.3 × 10 −9 ), time-to-dementia GS (Hazard ratio 1.24, 95% confidence interval 1.08–1.44, 0.003), but not LBC1936 1.11, 0.32). Conclusions might make contribution risk profile poor dementia, however these scores require replication further studies.

Language: Английский

Citations

3
Blood-based epigenome-wide analyses of chronic low-grade inflammation across diverse population cohorts DOI Creative Commons
Robert F. Hillary,

Hong Kiat Ng,

Daniel L. McCartney

et al.

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

Published: Nov. 3, 2023

Abstract Chronic inflammation is a hallmark of ageing and age-related disease states. The effectiveness inflammatory proteins such as C-reactive protein (CRP) in assessing long-term hindered by their phasic nature. DNA methylation (DNAm) signatures CRP may act more reliable markers chronic inflammation. We show that inter-individual differences DNAm capture 50% the variance circulating (N=17,936, Generation Scotland). develop series predictors using state-of-the-art algorithms. An elastic net regression-based predictor outperformed competing methods explained 18% phenotypic LBC1936 cohort, doubling existing predictors. performed comparably four additional test cohorts (ALSPAC, HELIOS, SABRE, LBC1921), including individuals diverse genetic ancestry from different age groups. newly-described surpassed assay-measured score its associations with 26 health outcomes. Our findings forge new avenues for low-grade populations.

Language: Английский

Citations

7
Epigenetics and bronchopulmonary dysplasia: unraveling the complex interplay and potential therapeutic implications DOI Creative Commons
Rui Song, Vineet Bhandari

Pediatric Research, Journal Year: 2024, Volume and Issue: 96(3), P. 567 - 568

Published: May 16, 2024

Language: Английский

Citations

2
The association between c-reactive protein and human brain microstructure: A systematic review of diffusion imaging studies DOI Creative Commons
Sanam Alilou,

Parya Valizadeh,

Sara KamaliZonouzi

et al.

Brain Behavior and Immunity Integrative, Journal Year: 2024, Volume and Issue: 8, P. 100092 - 100092

Published: Oct. 21, 2024

Language: Английский

Citations

1
Biomarkers of aging through the life course: a recent literature update DOI Creative Commons
Abigail Gaylord, Alan A. Cohen, Allison Kupsco

et al.

Current Opinion in Epidemiology and Public Health, Journal Year: 2023, Volume and Issue: 2(2), P. 7 - 17

Published: June 1, 2023

Purpose of review The development biomarkers aging has greatly advanced epidemiological studies processes. However, much debate remains on the timing onset and causal relevance these biomarkers. In this review, we discuss most recent that have been applied across life course. Recent findings recently developed course can be designated into three categories: epigenetic clocks, markers chronic inflammation, mitochondrial DNA copy number. Although at different stages, development, validation, application largely centered populations older adults. Few examined trajectories As wealth molecular biochemical data increases, emerging may able to capture complex system-specific Recently include novel clocks; clocks based ribosomal DNA, transcriptomic profiles, proteomics, metabolomics, inflammatory markers; clonal hematopoiesis indeterminate potential gene mutations; multiomics approaches. Summary Attention should placed early middle stages better understand Additionally, will provide greater insight specific mechanisms reflected by considered when interpreting results.

Language: Английский

Citations

1
Epigenetic scores derived in saliva are associated with gestational age at birth DOI Creative Commons
K. I. M. McKinnon, Eleanor L.S. Conole, Kadi Vaher

et al.

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

Published: June 29, 2024

Epigenetic scores (EpiScores), reflecting DNA methylation (DNAm)-based surrogates for complex traits, have been developed multiple circulating proteins. EpiScores pro-inflammatory proteins, such as C-reactive protein (DNAm CRP), are associated with brain health and cognition in adults inflammatory comorbidities of preterm birth neonates. Social disadvantage can become embedded child development through inflammation, deprivation is overrepresented infants. We tested the hypotheses that socioeconomic status (SES) alterations a set enriched inflammation-associated

Language: Английский

Citations

0
Prenatal exposure to common infections and newborn DNA methylation: A prospective, population-based study DOI Creative Commons
Anna Suleri, Kristina Salontaji, Mannan Luo

et al.

Brain Behavior and Immunity, Journal Year: 2024, Volume and Issue: 121, P. 244 - 256

Published: July 29, 2024

Infections during pregnancy have been robustly associated with adverse mental and physical health outcomes in offspring, yet the underlying molecular pathways remain largely unknown. Here, we examined whether exposure to common infections utero associates DNA methylation (DNAm) patterns at birth this turn relates offspring general population. Using data from 2,367 children Dutch population-based Generation R Study, first performed an epigenome-wide association study identify differentially methylated sites regions prenatal infection exposure. We also influence of timing by using self-reported cumulative scores for each trimester. Second, sought develop aggregate profile score (MPS) based on cord blood DNAm as epigenetic proxy tested MPS prospectively outcomes, including psychiatric symptoms, BMI, asthma ages 13–16 years. Third, investigated age acceleration – a marker biological aging. Across all analysis steps, our findings replicate 864 participants independent cohort (ALSPAC, UK). observed no or relation exposure, after multiple testing correction. 33 showed suggestive associations (p < 5e10 − 5; which one was nominally ALSPAC), indicating potential links genes immune, neurodevelopmental, cardiovascular pathways. While maternal reports internal hold out sample Study (R2incremental = 0.049), it did not ALSPAC 0.001), associate either cohort. Moreover, between across cohorts clocks. In contrast prior studies, reported differences exposed severe utero, do find evidence clinically evident aging within pediatric Future studies are needed establish exist but too subtle be statistically meaningful present sizes, they more similar discovery cohort, occur different tissues than blood, other may relevant mediating effect downstream outcomes.

Language: Английский

Citations

0