| Title: |
Genome-wide study of DNA methylation shows alterations in metabolic, inflammatory, and cholesterol pathways in ALS |
| Authors: |
Hop, Paul; Zwamborn, Ramona; Hannon, Eilis; Shireby, Gemma; Nabais, Marta; Walker, Emma; van Rheenen, Wouter; van Vugt, Joke; Dekker, Annelot; Westeneng, Henk-Jan; Tazelaar, Gijs; van Eijk, Kristel; Moisse, Matthieu; Baird, Denis; Al Khleifat, Ahmad; Iacoangeli, Alfredo; Ticozzi, Nicola; Ratti, Antonia; Cooper-Knock, Jonathan; Morrison, Karen; Shaw, Pamela; Basak, a Nazli; Chiò, Adriano; Chio, Adriano; Calvo, Andrea; Moglia, Cristina; Canosa, Antonio; Brunetti, Maura; Grassano, Maurizio; Gotkine, Marc; Lerner, Yossef; Zabari, Michal; Vourc’h, Patrick; Corcia, Philippe; Couratier, Philippe; Mora Pardina, Jesus; Salas, Teresa; Dion, Patrick; Ross, Jay; Henderson, Robert; Mathers, Susan; Mccombe, Pamela; Needham, Merrilee; Nicholson, Garth; Rowe, Dominic; Pamphlett, Roger; Mather, Karen; Sachdev, Perminder; Furlong, Sarah; Garton, Fleur; Henders, Anjali; Lin, Tian; Ngo, Shyuan; Steyn, Frederik; Wallace, Leanne; Williams, Kelly; Neto, Miguel Mitne; Cauchi, Ruben; Blair, Ian; Kiernan, Matthew; Drory, Vivian; Povedano, Monica; de Carvalho, Mamede; Pinto, Susana; Weber, Markus; Rouleau, Guy; Silani, Vincenzo; Landers, John; Shaw, Christopher; Andersen, Peter; Mcrae, Allan; van Es, Michael; Pasterkamp, R Jeroen; Wray, Naomi; Mclaughlin, Russell; Hardiman, Orla; Kenna, Kevin; Tsai, Ellen; Runz, Heiko; Al-Chalabi, Ammar; van den Berg, Leonard; van Damme, Philip; Mill, Jonathan; Veldink, Jan; Zwamborn, Ramona A.J.; van Vugt, Joke J.F.A.; Tazelaar, Gijs H.P.; Basak, A. Nazli; Pasterkamp, R. Jeroen; Heijmans, Bastiaan; T Hoen, Peter A.C.; van Meurs, Joyce; Jansen, Rick; Franke, Lude; Boomsma, Dorret; Pool, Rene; van Dongen, Jenny; Hottenga, Joukje; van Greevenbroek, Marleen M.J.; Stehouwer, Coen D.A.; van der Kallen, Carla J.H.; Schalkwijk, Casper; Wijmenga, Cisca; Zhernakova, Sasha; Tigchelaar, Ettje; Slagboom, P. Eline; Beekman, Marian; Deelen, Joris; van Heemst, Diana; van Duijn, Cornelia; Hofman, Bert; Isaacs, Aaron; Uitterlinden, Andre; Jhamai, P. Mila; Verbiest, Michael; Suchiman, H. Eka D.; Verkerk, Marijn; van der Breggen, Ruud; van Rooij, Jeroen; Lakenberg, Nico; Mei, Hailiang; van Iterson, Maarten; van Galen, Michiel; Bot, Jan; Zhernakova, Dasha; Deelen, Patrick; Nooren, Irene; Moed, Matthijs; Vermaat, Martijn; Luijk, Rene; Jan Bonder, Marc; van Dijk, Freerk; Arindrarto, Wibowo; Kielbasa, Szymon; Swertz, Morris; van Zwet, Erik; Bensimon, Gilbert; Smith, George Davey |
| Contributors: |
Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht; University Medical Center Utrecht (UMCU); Maurice Wohl Clinical Neuroscience Institut; King‘s College London; Institute of Psychiatry, Psychology & Neuroscience, King's College London; NIHR Biomedical Research Centre London; King‘s College London-Guy's and St Thomas' NHS Foundation Trust; Istituto Auxologico Italiano IRCCS Ospedale San Luca Milan, Italy (IAI); IRCCS Ospedale San Raffaele Milan, Italy; Centro Dino Ferrari Milano; Università degli Studi di Milano = University of Milan (UNIMI)-Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico; The Institute of Neuroscience Sheffield; University of Sheffield Sheffield; Koç University; Università degli studi di Torino = University of Turin (UNITO); Città della Salute e della Scienza di Torino (A.O.U); Centre Hospitalier Régional Universitaire de Tours (CHRU Tours); Imaging, Brain & Neuropsychiatry (iBraiN); Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM); ANR-13-JPRF-0003,STRENGTH,Survival, Trigger and Risk, Epigenetic, eNvironmental and Genetic Targets for motor neuron Health(2013); ANR-17-JPCD-0001,BRAIN-MEND,Biological Resource Analysis to Identify New MEchanisms and phenotypes in Neurodegenerative Diseases(2017) |
| Source: |
ISSN: 1946-6234. |
| Publisher Information: |
CCSD; American Association for the Advancement of Science (AAAS) |
| Publication Year: |
2022 |
| Collection: |
Université François-Rabelais de Tours: HAL |
| Subject Terms: |
MESH: Amyotrophic Lateral Sclerosis; MESH: Cholesterol; MESH: DNA Methylation; MESH: Epigenesis; Genetic; MESH: Genome-Wide Association Study; MESH: Humans; MESH: Neurodegenerative Diseases; [SDV]Life Sciences [q-bio] |
| Description: |
International audience ; 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/35196023; PUBMED: 35196023; PUBMEDCENTRAL: PMC10040186 |
| DOI: |
10.1126/scitranslmed.abj0264 |
| Availability: |
https://hal.science/hal-03939741; https://hal.science/hal-03939741v1/document; https://hal.science/hal-03939741v1/file/nihms-1869835.pdf; https://doi.org/10.1126/scitranslmed.abj0264 |
| Rights: |
info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.8CBC3723 |
| Database: |
BASE |