{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Hop PJ"],"funding":["Economic and Social Research Council","Medical Research Council","National Institute for Health Research (NIHR)","Motor Neurone Disease Association","NINDS NIH HHS","Health Research Board","Wellcome Trust"],"pagination":["eabj0264"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10040186"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["14(633)"],"pubmed_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 ma"],"journal":["Science translational medicine"],"pubmed_title":["Genome-wide study of DNA methylation shows alterations in metabolic, inflammatory, and cholesterol pathways in ALS."],"pmcid":["PMC10040186"],"funding_grant_id":["UKDRI-6001","NIHR202421","MCLAUGHLIN/OCT15/957-799","MC_PC_17115","Al-Chalabi/Nov19/110-950","MR/L021803/1","1095215","SHAW/APR18/864-791","R56 NS073873","G0300329","SHAW/NOV14/985-797","G0900635","G0600974","G1100695","R01 NS073873","Al-Chalabi/Apr19/870-791","NF-SI-0512-10082","McLaughlin/Apr21/879-791","NF-SI-0617-10077","MR/L501529/1","G0500289","216596/Z/19/Z","ES/L008238/1","G0500289B","ALCHALABI-DOBSON/APR14/829-791","G0900688","MR/R024804/1","JPI-JPND-2017-1"],"pubmed_authors":["Kielbasa SM","Lin T","Uitterlinden AG","Ratti A","van Galen M","McCombe PA","van der Kallen CJH","Swertz MA","Van Damme P","Williams KL","Furlong S","Blair IP","Kiernan MC","van Zwet EW","Brain MEND Consortium","Canosa A","Baird D","van der Breggen R","Arindrarto W","Zhernakova DV","Jhamai PM","Moisse M","Hardiman O","van 't Hof P","Rowe DB","Mora Pardina JS","Mill J","Landers JE","Franke L","Tazelaar GHP","Runz H","Zabari M","Schalkwijk CG","Beekman M","van Dongen J","Andersen PM","Lakenberg N","Povedano M","Silani V","Nooren I","van Vugt JJFA","Henders AK","Basak AN","van Meurs J","van Rheenen W","Jan Bonder M","Henderson RD","Shaw PJ","Boomsma DI","van Eijk KR","Iacoangeli A","Corcia P","Gotkine M","Stehouwer CDA","Verbiest M","Dion P","Garton FC","Verkerk M","Wijmenga C","Ross JP","Jansen R","Hop PJ","Moed M","Pasterkamp RJ","Cooper-Knock J","Pinto S","van den Berg LH","van Rooij J","Deelen P","Hofman BA","Kenna KP","Mathers S","Slagboom PE","Zwamborn RAJ","Couratier P","van Es MA","Shireby GL","Pamphlett R","Moglia C","Rouleau GA","Vourc'h P","Nicholson G","Shaw CE","Steyn FJ","Suchiman HED","Vermaat M","van Greevenbroek MMJ","van Duijn CM","Bensimon G","Tsai E","Al Khleifat A","Calvo A","van Dijk F","Deelen J","Walker EM","Drory V","Pool R","Wallace L","Ticozzi N","Wray NR","Sachdev PS","Dekker AM","Zhernakova S","Bot J","Westeneng HJ","Lerner Y","van Iterson M","Heijmans BT","Morrison KE","Hannon E","Isaacs A","McLaughlin RL","Needham M","Hottenga JJ","Weber M","Cauchi RJ","Grassano M","T Hoen PAC","Luijk R","Brunetti M","Nabais MF","Salas T","de Carvalho M","BIOS Consortium","Smith GD","Chio A","Ngo ST","McRae AF","Mather KA","Mei H","Tigchelaar EF","Al-Chalabi A","van Heemst D","Veldink JH","Neto MM"],"additional_accession":[]},"is_claimable":false,"name":"Genome-wide study of DNA methylation shows alterations in metabolic, inflammatory, and cholesterol pathways in ALS.","description":"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 ma","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Feb","modification":"2025-04-04T00:02:56.752Z","creation":"2025-04-04T00:02:56.752Z"},"accession":"S-EPMC10040186","cross_references":{"pubmed":["35196023"],"doi":["10.1126/scitranslmed.abj0264"]}}