Parkinson’s disease is associated with DNA methylation levels in human blood and saliva
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TLDR
This study demonstrates that PD status has a profound association with DNA methylation levels in blood and saliva; and the most significant PD-related changes reflect changes in blood cell composition.Abstract:
Several articles suggest that DNA methylation levels in blood relate to Parkinson’s disease (PD) but there is a need for a large-scale study that involves suitable population based controls. The purposes of the study were: (1) to study whether PD status is associated with DNA methylation levels in blood/saliva; (2) to study whether observed associations relate to blood cell types; and (3) to characterize genome-wide significant markers (“CpGs”) and clusters of CpGs (co-methylation modules) in terms of biological pathways. In a population-based case control study of PD, we studied blood samples from 335 PD cases and 237 controls and saliva samples from another 128 cases and 131 controls. DNA methylation data were generated from over 486,000 CpGs using the Illumina Infinium array. We identified modules of CpGs (clusters) using weighted correlation network analysis (WGCNA). Our cross-sectional analysis of blood identified 82 genome-wide significant CpGs (including cg02489202 in LARS2 p = 8.3 × 10–11 and cg04772575 in ABCB9 p = 4.3 × 10–10). Three out of six PD related co-methylation modules in blood were significantly enriched with immune system related genes. Our analysis of saliva identified five significant CpGs. PD-related CpGs are located near genes that relate to mitochondrial function, neuronal projection, cytoskeleton organization, systemic immune response, and iron handling. This study demonstrates that: (1) PD status has a profound association with DNA methylation levels in blood and saliva; and (2) the most significant PD-related changes reflect changes in blood cell composition. Overall, this study highlights the role of the immune system in PD etiology but future research will need to address the causal structure of these relationships.read more
Citations
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Journal ArticleDOI
Parkinson's Disease: Biomarkers, Treatment, and Risk Factors.
TL;DR: This review covers molecules that might act as the biomarkers of Parkinson's disease and suggests that microRNA-based analysis may bring considerable progress, especially if it is combined with α-syn data.
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DNA methylation in human diseases.
Zelin Jin,Yun Liu +1 more
TL;DR: Those promises and unique challenges of epigenetic epidemiological studies are described and some potential solutions are proposed to solve these challenges.
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Recalibrating the epigenetic clock: implications for assessing biological age in the human cortex
Gemma Shireby,Jonathan P. Davies,Paul T. Francis,Paul T. Francis,Joe Burrage,Emma Walker,Grant W. A. Neilson,Aisha Dahir,Alan J. Thomas,Seth Love,Rebecca G. Smith,Katie Lunnon,Meena Kumari,Leonard C. Schalkwyk,Kevin Morgan,Keeley J. Brookes,Eilis Hannon,Jonathan Mill +17 more
TL;DR: A novel epigenetic clock is developed that performs optimally in human cortical tissue and has the potential to identify phenotypes associated with biological ageing in the brain.
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The Search for Environmental Causes of Parkinson’s Disease: Moving Forward
Honglei Chen,Beate Ritz +1 more
TL;DR: Novel research hypotheses and approaches are speculated about that may help to better define the role of environment in PD etiology, especially during its extended and complex prodromal phase.
Journal ArticleDOI
DNA Methylation Signatures of Depressive Symptoms in Middle-aged and Elderly Persons: Meta-analysis of Multiethnic Epigenome-wide Studies.
O. Jovanova,Ivana Nedeljkovic,Derek Spieler,Rosie M. Walker,Chunyu Liu,Chunyu Liu,Michelle Luciano,Jan Bressler,Jennifer A. Brody,Amanda J. Drake,Kathryn L. Evans,Rahul Gondalia,Sonja Kunze,Brigitte Kühnel,Jari Lahti,Rozenn N. Lemaitre,Riccardo E. Marioni,Brenton R. Swenson,Jayandra J. Himali,Jayandra J. Himali,Hongsheng Wu,Yun Li,Allan F. McRae,Tom C. Russ,James A. Stewart,Zhiying Wang,Guosheng Zhang,Karl-Heinz Ladwig,André G. Uitterlinden,Xiuqing Guo,Annette Peters,Katri Räikkönen,John M. Starr,Melanie Waldenberger,Naomi R. Wray,Eric A. Whitsel,Nona Sotoodehnia,Sudha Seshadri,Sudha Seshadri,David J. Porteous,Joyce B. J. van Meurs,Thomas H. Mosley,Andrew M. McIntosh,Michael M. Mendelson,Michael M. Mendelson,Daniel Levy,Lifang Hou,Johan G. Eriksson,Myriam Fornage,Ian J. Deary,Andrea A. Baccarelli,Henning Tiemeier,Henning Tiemeier,Najaf Amin +53 more
TL;DR: This first cross-ethnic meta-analysis of epigenome-wide association studies (EWAS) within the framework of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium identifies 3 methylated sites associated with depressive symptoms.
References
More filters
Journal ArticleDOI
WGCNA: an R package for weighted correlation network analysis.
Peter Langfelder,Steve Horvath +1 more
TL;DR: The WGCNA R software package is a comprehensive collection of R functions for performing various aspects of weighted correlation network analysis that includes functions for network construction, module detection, gene selection, calculations of topological properties, data simulation, visualization, and interfacing with external software.
Journal ArticleDOI
Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases.
TL;DR: The pathological findings in 100 patients diagnosed prospectively by a group of consultant neurologists as having idiopathic Parkinson's disease are reported, and these observations call into question current concepts of Parkinson's Disease as a single distinct morbid entity.
Journal ArticleDOI
A General Framework for Weighted Gene Co-Expression Network Analysis
Bin Zhang,Steve Horvath +1 more
TL;DR: A general framework for `soft' thresholding that assigns a connection weight to each gene pair is described and several node connectivity measures are introduced and provided empirical evidence that they can be important for predicting the biological significance of a gene.
Journal ArticleDOI
DNA methylation age of human tissues and cell types
TL;DR: It is proposed that DNA methylation age measures the cumulative effect of an epigenetic maintenance system, and can be used to address a host of questions in developmental biology, cancer and aging research.
Journal ArticleDOI
Systematic review of levodopa dose equivalency reporting in Parkinson's disease
TL;DR: A systematic review of studies reporting LEDs yielded a standardized LED for each drug, providing a useful tool to express dose intensity of different antiparkinsonian drug regimens on a single scale.
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