![]() 2012.0091, 2014.0305, and 2020.0232 to P.M.A.), the Ulla-Carin Lindquist Foundation and the Västerbotten County Council (grant no. 100 to P.M.A.), the Knut and Alice Wallenberg Foundation (grant nos. 772376-EScORIAL to J.H.V.), the Swedish Brain Foundation (grant nos. and J.H.V.), The Canadian Institutes of Health Research (FRN 159279 to J.P.R.), The Dutch Research Council (NWO) (VIDI grant 91719350 to K.P.K.), The European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement no. The research reported in this publication was supported by grants from The Dutch Research Council (NWO) (VENI scheme grant 09150161810018 to W.v.R.) and Prinses Beatrix Spierfond (neuromuscular fellowship grant W.F19-03 to W.v.R.), The Prinses Beatrix Spierfonds (W.OR20-08 to J.J.F.A.v.V. ![]() 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. Integration of these results with our latest genome-wide association study showed that cholesterol biosynthesis was potentially causally related to ALS. 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. 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. Here, we present a blood-based epigenome-wide association study meta-analysis in 9706 samples passing stringent quality control (6763 patients, 2943 controls). 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. ![]() Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an estimated heritability between 40 and 50%.
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