Genome-wide study of DNA methylation shows alterations in metabolic, inflammatory, and cholesterol pathways in ALS

Paul J. Hop, Ramona A.J. Zwamborn, Eilís Hannon, Gemma Shireby, Marta F. Nabais, Emma Walker, Wouter van Rheenen, Joke J.F.A. van Vugt, Annelot M. Dekker, Henk‐Jan Westeneng, Gijs H.P. Tazelaar, Kristel R. van Eijk, Matthieu Moisse, Denis Baird, Ahmad Al Khleifat, Alfredo Iacoangeli, Nicola Ticozzi, Antonia Ratti, Johnathan Cooper‐Knock, Karen Morrison, Pamela J. Shaw, A. Nazlı Başak, Adriano Chiò, Andrea Calvo, Cristina Moglia, Antonio Canosa, Maura Brunetti, Maurizio Grassano, Marc Gotkine, Yossef Lerner, Michal Zabari, Patrick Vourc’h, Philippe Corcia, P. Couratier, Jesús S. Mora Pardina, Teresa Salas, Patrick A. Dion, Jay P. Ross, Robert D. Henderson, Susan Mathers, Pamela A. McCombe, Merrilee Needham, Garth Nicholson, Dominic B. Rowe, Roger Pamphlett, Karen A. Mather, Perminder S. Sachdev, Sarah Furlong, Fleur C. Garton, Anjali K. Henders, Tian Lin, Shyuan T. Ngo, Frederik J. Steyn, Leanne Wallace, Kelly L. Williams, Miguel Mitne Neto, Ruben J. Cauchi, Ian P. Blair, Matthew C. Kiernan, Vivian Drory, Mónica Povedano, Mamede de Carvalho, Susana Pinto, Markus Weber, Guy A. Rouleau, Vincenzo Silani, John E. Landers, Christopher E. Shaw, Peter M. Andersen, Allan F. McRae, Michael A. van Es, R. Jeroen Pasterkamp, Naomi R. Wray, Russell L. McLaughlin, Orla Hardiman, Kevin P. Kenna, Ellen Tsai, Heiko Runz, Ammar Al‐Chalabi, Leonard H. van den Berg, Philip Van Damme, Jonathan Mill, Jan H. Veldink, Bastiaan T. Heijmans, Peter A.C. t Hoen, Joyce van Meurs, Rick Jansen, Lude Franke, Dorret I. Boomsma, René Pool, Jenny van Dongen, Joukje J. Hottenga, Marleen M. J. van Greevenbroek, Coen D.A. Stehouwer, Carla Kallen, Casper G. Schalkwijk, Cisca Wijmenga, Lude Franke, Sasha Zhernakova, Ettje F. Tigchelaar

Science Translational Medicine · 2022

Read source ↗ All evidence

Summary

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

Source type: Peer-reviewed study
DOI: 10.1126/scitranslmed.abj0264
Catalogue ID: SNmoj7ntfg-rkwng8

Pulse AI · ask about this record

Dig deeper with Pulse AI.

Pulse AI has read the whole catalogue. Ask about this record, its theme, or how the findings apply to UK farming and policy — every answer cites the underlying studies.

How does this finding apply in a UK context?→What are the most cited records on this topic?→