SynthesisScience translational medicine2022
Genome-wide study of DNA methylation shows alterations in metabolic, inflammatory, and cholesterol pathways in ALS.
Open access · greenAbstract readMeta-Analysis
In one paragraph
Synthesis in Science translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed, 1 pooled it
10.5field-weighted citation impact, top 1% of its field
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
66 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.
- L-Carnitine in the Treatment of Psychiatric and Neurological Manifestations: A Systematic Review.Nutrients · 2024Pooled it
- Genetically Predicted Blood DNA Methylation Reveals Putative Regulatory Signals Associated with ALS Risk.medRxiv : the preprint server for health sciences · 2026Article
- Clonal CD8 T cells link peripheral and intrathecal immunity in ALS4 progression: a multiomics reference for ALS.Research square · 2026Article
- Cholesterol in amyotrophic lateral sclerosis: a bystander, a biomarker, or a target?Atherosclerosis plus · 2026Review
- Sex-aware causal inference assessment of the immune system in complex neurodegenerative diseases.Brain : a journal of neurology · 2026Article
- Strategic Amyotrophic Lateral Sclerosis Australia-Systems Genomics Consortium (SALSA-SGC): cohort profile.BMJ open · 2026Article
- Multimodal analysis of cell-free DNA identifies epigenetic biomarkers for amyotrophic lateral sclerosis diagnosis and progression.The Journal of clinical investigation · 2026Article
- CpGene: a web application for epigenetic signature identification from DNA methylation arrays.Bioinformatics (Oxford, England) · 2026Article
- Multimodal analysis of cell-free DNA identifies epigenetic biomarkers for amyotrophic lateral sclerosis diagnosis and progression.bioRxiv : the preprint server for biology · 2026Article
- Disruption of the angiopoietin-like system connects lipid homeostasis and hypothalamic dysfunction in ALS.BMC medicine · 2026Article
- Prevalence and impact of comorbidities in amyotrophic lateral sclerosis.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- A multi-omics study on monozygotic twins discordant for amyotrophic lateral sclerosis and literature review underline a potential role for innate immunity and epigenetic dysregulation in disease mechanisms.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Review
- Disrupted astrocyte-neuron metabolic coupling in amyotrophic lateral sclerosis.Frontiers in cell and developmental biology · 2026Review
- Astrocyte epigenetics in development, aging, and neurodegeneration: a DNA methylation perspective.Frontiers in molecular neuroscience · 2026Review
- Association of DRD4 promoter-associated methylation with mild cognitive impairment in Han and Uygur populations.European journal of medical research · 2025Article
- Dissecting epigenetic age acceleration in amyotrophic lateral sclerosis.Epigenomics · 2025Article
- Function of epigenetic modifications in wound healing and potential therapies (Review).International journal of molecular medicine · 2025Review
- Entering the era of precision medicine to treat amyotrophic lateral sclerosis.Molecular neurodegeneration · 2025Review
- Epigenetic profiles of tissue informative CpGs inform ALS disease status and progression.Genome medicine · 2025Article
- Iron and Ferritin Dyshomeostasis Intersect with Sex, Age, and Disease Severity in Amyotrophic Lateral Sclerosis.Journal of molecular neuroscience : MN · 2025Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
85 authors at 20 institutions in 17 countries.
Paul J HopDepartment of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht 3584 CX, Netherlands.ORCID 0000-0002-9007-7436
Ramona A J ZwambornDepartment of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht 3584 CX, Netherlands.ORCID 0000-0003-3952-5042
Eilis HannonUniversity of Exeter Medical School, College of Medicine and Health, University of Exeter, Exeter EX1 2LU, UK.ORCID 0000-0001-6840-072X
Gemma L ShirebyUniversity of Exeter Medical School, College of Medicine and Health, University of Exeter, Exeter EX1 2LU, UK.ORCID 0000-0002-8238-0080
Marta F NabaisUniversity of Exeter Medical School, College of Medicine and Health, University of Exeter, Exeter EX1 2LU, UK.ORCID 0000-0002-9545-5889
Emma M WalkerUniversity of Exeter Medical School, College of Medicine and Health, University of Exeter, Exeter EX1 2LU, UK.ORCID 0000-0003-2222-4577
Wouter van RheenenDepartment of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht 3584 CX, Netherlands.ORCID 0000-0002-5860-1533
Joke J F A van VugtDepartment of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht 3584 CX, Netherlands.ORCID 0000-0002-4161-4004
Annelot M DekkerDepartment of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht 3584 CX, Netherlands.
Henk-Jan WestenengDepartment of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht 3584 CX, Netherlands.
Gijs H P TazelaarDepartment of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht 3584 CX, Netherlands.
Kristel R van EijkDepartment of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht 3584 CX, Netherlands.
Matthieu MoisseKU Leuven-University of Leuven, Department of Neurosciences, Experimental Neurology and Leuven Brain Institute (LBI), Leuven 3000, Belgium.ORCID 0000-0001-8880-9311
Denis BairdTranslational Biology, Biogen, Boston, MA 02142, USA.
Ahmad Al KhleifatMaurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, UK.
Alfredo IacoangeliMaurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, UK.
Nicola TicozziDepartment of Neurology-Stroke Unit and Laboratory of Neuroscience, Istituto Auxologico Italiano IRCCS, Milan 20149, Italy.ORCID 0000-0001-5963-7426
Antonia RattiDepartment of Neurology-Stroke Unit and Laboratory of Neuroscience, Istituto Auxologico Italiano IRCCS, Milan 20149, Italy.ORCID 0000-0002-4264-6614
Jonathan Cooper-KnockSheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield S10 2HQ, UK.ORCID 0000-0002-0873-8689
Karen E MorrisonSchool of Medicine, Dentistry, and Biomedical Sciences, Queen's University Belfast, Belfast BT9 7BL, UK.ORCID 0000-0003-0216-5717
Pamela J ShawSheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield S10 2HQ, UK.ORCID 0000-0002-8925-2567
A Nazli BasakKoc University, School of Medicine, Translational Medicine Research Center, NDAL, Istanbul, 34450, Turkey.ORCID 0000-0001-6977-2517
Adriano Chiò"Rita Levi Montalcini" Department of Neuroscience, ALS Centre, University of Torino, Turin 10126, Italy.ORCID 0000-0001-9579-5341
Andrea Calvo"Rita Levi Montalcini" Department of Neuroscience, ALS Centre, University of Torino, Turin 10126, Italy.ORCID 0000-0002-5122-7243
Cristina Moglia"Rita Levi Montalcini" Department of Neuroscience, ALS Centre, University of Torino, Turin 10126, Italy.ORCID 0000-0001-7377-7222
Antonio Canosa"Rita Levi Montalcini" Department of Neuroscience, ALS Centre, University of Torino, Turin 10126, Italy.ORCID 0000-0001-5876-4079
Maura Brunetti"Rita Levi Montalcini" Department of Neuroscience, ALS Centre, University of Torino, Turin 10126, Italy.
Maurizio Grassano"Rita Levi Montalcini" Department of Neuroscience, ALS Centre, University of Torino, Turin 10126, Italy.ORCID 0000-0001-6714-6897
Marc GotkineFaculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91904, Israel.ORCID 0000-0003-2541-6232
Yossef LernerFaculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Michal ZabariFaculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Patrick Vourc'hService de Biochimie et Biologie moléculaire, CHU de Tours, Tours 37044, France.ORCID 0000-0001-7960-8139
Philippe CorciaUMR 1253, Université de Tours, Inserm, Tours 37044, France.
Philippe CouratierCentre de référence sur la SLA, CHRU de Limoges, Limoges 87042, France.
Jesus S Mora PardinaALS Unit, Hospital San Rafael, Madrid, Spain.ORCID 0000-0001-6633-5354
Teresa SalasDepartment of Neurology, Hospital La Paz-Carlos III, Madrid 28046, Spain.ORCID 0000-0002-8323-6371
Patrick DionMontréal Neurological Institute and Hospital, McGill University, Montréal, QC H3A 2B4, Canada.
Jay P RossMontréal Neurological Institute and Hospital, McGill University, Montréal, QC H3A 2B4, Canada.ORCID 0000-0002-8183-2524
Robert D HendersonDepartment of Neurology, Royal Brisbane and Women's Hospital, Brisbane, QLD 4029, Australia.ORCID 0000-0002-2820-8183
Susan MathersCalvary Health Care Bethlehem, Parkdale, VIC 3195, Australia.
Pamela A McCombeCentre for Clinical Research, University of Queensland, Brisbane, QLD 4019, Australia.
Merrilee NeedhamFiona Stanley Hospital, Perth, WA 6150, Australia.
Garth NicholsonANZAC Research Institute, Concord Repatriation General Hospital, Sydney, NSW 2139, Australia.
Dominic B RoweCentre for Motor Neuron Disease Research, Macquarie University, NSW 2109, Australia.ORCID 0000-0003-0912-2146
Roger PamphlettDiscipline of Pathology and Department of Neuropathology, Brain and Mind Centre, University of Sydney, Sydney, NSW 2050, Australia.ORCID 0000-0003-3326-7273
Karen A MatherCentre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, NSW 2031, Australia.ORCID 0000-0003-4143-8941
Perminder S SachdevCentre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, NSW 2031, Australia.ORCID 0000-0002-9595-3220
Sarah FurlongCentre for Motor Neuron Disease Research, Macquarie University, NSW 2109, Australia.
Fleur C GartonInstitute for Molecular Bioscience, University of Queensland, Brisbane, QLD4072, Australia.
Anjali K HendersInstitute for Molecular Bioscience, University of Queensland, Brisbane, QLD4072, Australia.ORCID 0000-0003-3672-1451
Tian LinInstitute for Molecular Bioscience, University of Queensland, Brisbane, QLD4072, Australia.
Shyuan T NgoCentre for Clinical Research, University of Queensland, Brisbane, QLD 4019, Australia.
Frederik J SteynCentre for Clinical Research, University of Queensland, Brisbane, QLD 4019, Australia.
Leanne WallaceInstitute for Molecular Bioscience, University of Queensland, Brisbane, QLD4072, Australia.ORCID 0000-0003-4310-7572
Kelly L WilliamsCentre for Motor Neuron Disease Research, Macquarie University, NSW 2109, Australia.ORCID 0000-0001-6319-9473
BIOS Consortium
Brain MEND Consortium
Miguel Mitne NetoUniversidade de São Paulo, São Paulo 05508-070, Brazil.
Ruben J CauchiCenter for Molecular Medicine and Biobanking and Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, 2023 Msida, Malta.ORCID 0000-0001-6150-1608
Ian P BlairCentre for Motor Neuron Disease Research, Macquarie University, NSW 2109, Australia.
Matthew C KiernanBrain and Mind Centre, University of Sydney, Sydney, NSW, 2050, Australia.ORCID 0000-0001-9054-026X
Vivian DroryDepartment of Neurology, Tel-Aviv Sourasky Medical Centre, Tel-Aviv 64239, Israel.
Monica PovedanoFunctional Unit of Amyotrophic Lateral Sclerosis (UFELA), Service of Neurology, Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona 08907, Spain.
Mamede de CarvalhoInstituto de Fisiologia, Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon 1649-028, Portugal.ORCID 0000-0001-7556-0158
Susana PintoInstituto de Fisiologia, Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon 1649-028, Portugal.ORCID 0000-0002-0727-5897
Markus WeberNeuromuscular Diseases Unit/ALS Clinic, Kantonsspital St. Gallen, 9007 St. Gallen, Switzerland.ORCID 0000-0002-5538-9274
Guy A RouleauMontréal Neurological Institute and Hospital, McGill University, Montréal, QC H3A 2B4, Canada.
Vincenzo SilaniDepartment of Neurology-Stroke Unit and Laboratory of Neuroscience, Istituto Auxologico Italiano IRCCS, Milan 20149, Italy.ORCID 0000-0002-7698-3854
John E LandersDepartment of Neurology, University of Massachusetts Medical School, Worcester, MA 01655, USA.ORCID 0000-0001-8084-5043
Christopher E ShawMaurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, UK.ORCID 0000-0003-0251-0146
Peter M AndersenDepartment of Clinical Science, Umeå University, Umeå SE-901 85, Sweden.ORCID 0000-0003-0094-5429
Allan F McRaeInstitute for Molecular Bioscience, University of Queensland, Brisbane, QLD4072, Australia.ORCID 0000-0001-5286-5485
Michael A van EsDepartment of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht 3584 CX, Netherlands.
R Jeroen PasterkampDepartment of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, 3584 CX, Netherlands.
Naomi R WrayInstitute for Molecular Bioscience, University of Queensland, Brisbane, QLD4072, Australia.ORCID 0000-0001-7421-3357
Russell L McLaughlinComplex Trait Genomics Laboratory, Smurfit Institute of Genetics, Trinity College Dublin, Dublin D02 PN40, Ireland.ORCID 0000-0003-3915-2135
Orla HardimanAcademic Unit of Neurology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin D02 PN40, Ireland.ORCID 0000-0003-2610-1291
Kevin P KennaDepartment of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht 3584 CX, Netherlands.
Ellen TsaiTranslational Biology, Biogen, Boston, MA 02142, USA.ORCID 0000-0002-5625-1189
Heiko RunzTranslational Biology, Biogen, Boston, MA 02142, USA.ORCID 0000-0002-2133-7345
Ammar Al-ChalabiMaurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, UK.ORCID 0000-0002-4924-7712
Leonard H van den BergDepartment of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht 3584 CX, Netherlands.ORCID 0000-0002-6559-3965
Philip Van DammeKU Leuven-University of Leuven, Department of Neurosciences, Experimental Neurology and Leuven Brain Institute (LBI), Leuven 3000, Belgium.ORCID 0000-0002-4010-2357
Jonathan MillUniversity of Exeter Medical School, College of Medicine and Health, University of Exeter, Exeter EX1 2LU, UK.ORCID 0000-0003-1115-3224
Jan H VeldinkDepartment of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht 3584 CX, Netherlands.ORCID 0000-0001-5572-9657
University Medical Center Utrecht · NLThe University of Queensland · AULeiden University Medical Center · NLMontreal Neurological Institute and Hospital · CAAzienda Ospedaliera Citta' della Salute e della Scienza di Torino · ITKing's College London · GBUniversity of Exeter · GBHebrew University of Jerusalem · ILMacquarie University · AUQueen's University Belfast · GBUniversity Medical Center Groningen · NLUniversity of Milan · ITBiogen (United States) · USTrinity College Dublin · IEAllen Institute for Brain Science · USErasmus University Rotterdam · NLRoyal Brisbane and Women's Hospital · AUThe University of Sydney · AUUmeå University · SEUniversité de Tours · FR
Funding
Identification of genes causative for familial ALS gene using exome sequencingR01NS073873 · NINDS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI LANDERS, JOHN E · 2011 to 2019
$4.6MIdentification and Characterization of ALS/FTD Associated Variants Using Whole Genome SequencingR56NS073873 · NINDS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI LANDERS, JOHN E · 2020 to 2020
$586kDepartment of HealthMedical Research Council G0300329Medical Research Council G0500289Medical Research Council G0600974Medical Research Council G0900635Medical Research Council G0900688Medical Research Council G1100695Medical Research Council MC_PC_17115Medical Research Council MR/L021803/1Medical Research Council MR/L501529/1Medical Research Council MR/R024804/1Motor Neurone Disease Association ALCHALABI-DOBSON/APR14/829-791Motor Neurone Disease Association MCLAUGHLIN/OCT15/957-799Motor Neurone Disease Association SHAW/APR18/864-791Motor Neurone Disease Association SHAW/NOV14/985-797NINDS NIH HHS R01 NS073873NINDS NIH HHS R56 NS073873Wellcome Trust
Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an estimated heritability between 40 and 50%. DNA methylation patterns can serve as proxies of (past) exposures and disease progression, as well as providing a potential mechanism that mediates genetic or environmental risk. Here, we present a blood-based epigenome-wide association study meta-analysis in 9706 samples passing stringent quality control (6763 patients, 2943 controls). We identified a total of 45 differentially methylated positions (DMPs) annotated to 42 genes, which are enriched for pathways and traits related to metabolism, cholesterol biosynthesis, and immunity. We then tested 39 DNA methylation-based proxies of putative ALS risk factors and found that high-density lipoprotein cholesterol, body mass index, white blood cell proportions, and alcohol intake were independently associated with ALS. Integration of these results with our latest genome-wide association study showed that cholesterol biosynthesis was potentially causally related to ALS. Last, DNA methylation at several DMPs and blood cell proportion estimates derived from DNA methylation data were associated with survival rate in patients, suggesting that they might represent indicators of underlying disease processes potentially amenable to therapeutic interventions.
Indexed as
Amyotrophic Lateral SclerosisNeurodegenerative DiseasesCholesterolDNA MethylationEpigenesis, GeneticGenome-Wide Association StudyHumansCholesterol
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