Epigenetic Association Analyses and Risk Prediction of RLS DOI Creative Commons

Philip Harrer,

Nazanin Mirza‐Schreiber, Vanessa Mandel

et al.

Movement Disorders, Journal Year: 2023, Volume and Issue: 38(8), P. 1410 - 1418

Published: May 22, 2023

ABSTRACT Background As opposed to other neurobehavioral disorders, epigenetic analyses and biomarkers are largely missing in the case of idiopathic restless legs syndrome (RLS). Objectives Our aims were develop a biomarker for RLS based on DNA methylation blood examine brain tissues dissecting pathophysiology. Methods Methylation from three independent cohorts (n = 2283) post‐mortem two 61) was assessed by Infinium EPIC 850 K BeadChip. Epigenome‐wide association study (EWAS) results individual combined random‐effect meta‐analysis. A three‐stage selection procedure (discovery, n 884; testing, 520; validation, 879) established an risk score including 30 CpG sites. Epigenetic age Horvath's multi‐tissue clock Shireby's cortical clock. Results EWAS meta‐analysis revealed 149 sites linked 136 genes ( P < 0.05 after Bonferroni correction) 23 18 (false discovery rate [FDR] 5%). Gene‐set suggested enrichments tissue types subunits kainate‐selective glutamate receptor complex. Individual candidate could be assigned neurodevelopmental or metabolic traits. The achieved area under curve (AUC) 0.70 (0.67–0.73) validation set, comparable analogous scores disorders. significant difference biological patients not detectable. Conclusions supports notion altered neurodevelopment RLS. reliably associated with but require even higher accuracy useful as biomarkers. © 2023 Authors. Movement Disorders published Wiley Periodicals LLC behalf International Parkinson Disorder Society.

Language: Английский

Assessing causal associations between neurodegenerative diseases and neurological tumors with biological aging: a bidirectional Mendelian randomization study DOI Creative Commons
Zhiyun Zhang,

Ningfang Liu,

Xuyang Pan

et al.

Frontiers in Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: Dec. 19, 2023

Background Aging is a significant risk factor for many neurodegenerative diseases and neurological tumors. Previous studies indicate that the frailty index, facial aging, telomere length (TL), epigenetic aging clock acceleration are commonly used biological proxy indicators. This study aims to comprehensively explore potential relationships between tumors by integrating various indicators, employing Mendelian randomization (MR) analysis. Methods Two-sample bidirectional MR analyses were conducted using genome-wide association (GWAS) data. Summary statistics tumors, along with obtained from extensive meta-analyses of GWAS. Genetic single-nucleotide polymorphisms (SNPs) associated exposures as instrumental variables, assessing causal three (Alzheimer’s disease, Parkinson’s amyotrophic lateral sclerosis), two benign (vestibular schwannoma meningioma), one malignant tumor (glioma), four indicators (frailty TL, acceleration). Sensitivity also performed. Results Our analysis revealed genetically predicted longer TL reduces Alzheimer’s disease but increases vestibular glioma (All Glioma, GBM, non-GBM). In addition, there suggestive relationship some (PD GBM) DNA methylation GrimAge acceleration. Causal other not observed. Conclusion Building upon prior investigations into telomeres our validates these findings larger GWAS data demonstrates, first time, GBM may promote age research provides new insights evidence

Language: Английский

Citations

6
Complementary value of molecular, phenotypic, and functional aging biomarkers in dementia prediction DOI Creative Commons
Andreas Engvig, Karl Trygve Kalleberg, Lars T. Westlye

et al.

GeroScience, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 24, 2024

Abstract DNA methylation age (MA), brain (BA), and frailty index (FI) are putative aging biomarkers linked to dementia risk. We investigated their relationship combined potential for prediction of cognitive impairment future risk using the ADNI database. Of several MA algorithms, DunedinPACE GrimAge2, associated with memory, were in a composite alongside BA data-driven FI predictive analyses. Pairwise correlations between age- sex-adjusted measures (aMA), aBA, aFI low. outperformed all diagnostic tasks. A model including age, sex, achieved an area under curve (AUC) 0.94 differentiating cognitively normal controls (CN) from patients held-out test set. When clinical (apolipoprotein E ε4 allele count, executive function), aBA predicted 5-year among MCI out-of-sample AUC 0.88. In prognostic model, offered complementary value (both β s 0.50). The tested MAs did not improve predictions. Results consistent across health deficit selection yielding best performance. had stronger adverse effect on prognosis males, while BA’s impact was greater females. Our findings highlight prediction. results support multidimensional view dementia, intertwined biomarkers, prognosis. MA’s limited contribution suggests caution use individual assessment dementia.

Language: Английский

Citations

1
Accelerated biological aging: unveiling the path to cardiometabolic multimorbidity, dementia, and mortality DOI Creative Commons

Yi He,

Jia Yu, Yizhou Li

et al.

Frontiers in Public Health, Journal Year: 2024, Volume and Issue: 12

Published: Oct. 30, 2024

Cardiometabolic multimorbidity (CMM) and aging are increasing public health concerns. This prospective study used UK Biobank cohort to investigate the relationship between biological trajectory of CMM dementia mortality.

Language: Английский

Citations

1
The Pace of Biological Aging Partially Explains the Relationship Between Socioeconomic Status and Chronic Low Back Pain Outcomes DOI Creative Commons
Edwin N. Aroke,

Jai Ganesh Nagidi,

Vinodh Srinivasasainagendra

et al.

Journal of Pain Research, Journal Year: 2024, Volume and Issue: Volume 17, P. 4317 - 4329

Published: Dec. 1, 2024

Having a lower socioeconomic status (SES) is predictor of age-related chronic conditions, including low back pain (cLBP). We aimed to examine whether the pace biological aging mediates relationship between SES and cLBP outcomes - intensity, interference, physical performance.

Language: Английский

Citations

1
Epigenetic Association Analyses and Risk Prediction of RLS DOI Creative Commons

Philip Harrer,

Nazanin Mirza‐Schreiber, Vanessa Mandel

et al.

Movement Disorders, Journal Year: 2023, Volume and Issue: 38(8), P. 1410 - 1418

Published: May 22, 2023

ABSTRACT Background As opposed to other neurobehavioral disorders, epigenetic analyses and biomarkers are largely missing in the case of idiopathic restless legs syndrome (RLS). Objectives Our aims were develop a biomarker for RLS based on DNA methylation blood examine brain tissues dissecting pathophysiology. Methods Methylation from three independent cohorts (n = 2283) post‐mortem two 61) was assessed by Infinium EPIC 850 K BeadChip. Epigenome‐wide association study (EWAS) results individual combined random‐effect meta‐analysis. A three‐stage selection procedure (discovery, n 884; testing, 520; validation, 879) established an risk score including 30 CpG sites. Epigenetic age Horvath's multi‐tissue clock Shireby's cortical clock. Results EWAS meta‐analysis revealed 149 sites linked 136 genes ( P < 0.05 after Bonferroni correction) 23 18 (false discovery rate [FDR] 5%). Gene‐set suggested enrichments tissue types subunits kainate‐selective glutamate receptor complex. Individual candidate could be assigned neurodevelopmental or metabolic traits. The achieved area under curve (AUC) 0.70 (0.67–0.73) validation set, comparable analogous scores disorders. significant difference biological patients not detectable. Conclusions supports notion altered neurodevelopment RLS. reliably associated with but require even higher accuracy useful as biomarkers. © 2023 Authors. Movement Disorders published Wiley Periodicals LLC behalf International Parkinson Disorder Society.

Language: Английский

Citations

3