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dc.contributor.authorROONEY, JAMESen
dc.contributor.authorHARDIMAN, ORLAen
dc.date.accessioned2015-02-13T15:09:43Z
dc.date.available2015-02-13T15:09:43Z
dc.date.issued2014en
dc.date.submitted2014en
dc.identifier.citationAmmar Al-Chalabi, Andrea Calvo, Adriano Chio, Shuna Colville, Cathy M Ellis, Orla Hardiman, Mark Heverin, Robin S Howard, Mark H B Huisman, Noa Keren, P Nigel Leigh, Letizia Mazzini, Gabriele Mora, Richard W Orrell, James Rooney, Kirsten M Scott, William J Scotton, Meinie Seelen, Christopher E Shaw, Katie S Sidle, Robert Swingler, Miho Tsuda, Jan H Veldink, Anne E Visser, Leonard H van den Berg, Neil Pearce, Analysis of amyotrophic lateral sclerosis as a multistep process: a population-based modelling study, The Lancet Neurology, 13, 11, 2014, 1108 - 1113en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/73206
dc.descriptionPUBLISHEDen
dc.description.abstractBackground Amyotrophic lateral sclerosis shares characteristics with some cancers, such as onset being more common in later life, progression usually being rapid, the disease affecting a particular cell type, and showing complex inheritance. We used a model originally applied to cancer epidemiology to investigate the hypothesis that amyotrophic lateral sclerosis is a multistep process. Methods We generated incidence data by age and sex from amyotrophic lateral sclerosis population registers in Ireland (registration dates 1995–2012), the Netherlands (2006–12), Italy (1995–2004), Scotland (1989–98), and England (2002–09), and calculated age and sex-adjusted incidences for each register. We regressed the log of age-specific incidence against the log of age with least squares regression. We did the analyses within each register, and also did a combined analysis, adjusting for register. Findings We identified 6274 cases of amyotrophic lateral sclerosis from a catchment population of about 34 million people. We noted a linear relationship between log incidence and log age in all five registers: England r2=0·95, Ireland r2=0·99, Italy r2=0·95, the Netherlands r2=0·99, and Scotland r2=0·97; overall r2=0·99. All five registers gave similar estimates of the linear slope ranging from 4·5 to 5·1, with overlapping confidence intervals. The combination of all five registers gave an overall slope of 4·8 (95% CI 4·5–5·0), with similar estimates for men (4·6, 4·3–4·9) and women (5·0, 4·5–5·5). Interpretation A linear relationship between the log incidence and log age of onset of amyotrophic lateral sclerosis is consistent with a multistage model of disease. The slope estimate suggests that amyotrophic lateral sclerosis is a six-step process. Identification of these steps could lead to preventive and therapeutic avenues.en
dc.description.sponsorshipFunding UK Medical Research Council; UK Economic and Social Research Council; Ireland Health Research Board; The Netherlands Organisation for Health Research and Development (ZonMw); the Ministry of Health and Ministry of Education, University, and Research in Italy; the Motor Neurone Disease Association of England, Wales, and Northern Ireland; and the European Commission (Seventh Framework Programme).en
dc.format.extent1108en
dc.format.extent1113en
dc.language.isoenen
dc.relation.ispartofseriesThe Lancet Neurologyen
dc.relation.ispartofseries13en
dc.relation.ispartofseries11en
dc.rightsYen
dc.subjectAmyotrophic lateral sclerosis sen
dc.subject.lcshAmyotrophic lateral sclerosis sen
dc.titleAnalysis of amyotrophic lateral sclerosis as a multistep process: a population-based modelling studyen
dc.typeJournal Articleen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/rooneyj4en
dc.identifier.peoplefinderurlhttp://people.tcd.ie/hardimaoen
dc.identifier.rssinternalid100162en
dc.identifier.doihttp://dx.doi.org/10.1016/S1474-4422(14)70219-4en
dc.rights.ecaccessrightsopenAccess
dc.subject.TCDThemeAgeingen
dc.subject.TCDThemeNeuroscienceen
dc.subject.TCDTagAge related diseasesen
dc.subject.TCDTagAmyotrophic Lateral Sclerosis (ALS)en
dc.subject.TCDTagEpidemiologyen
dc.subject.TCDTagSTATISTICAL-MODELSen
dc.identifier.rssurihttp://www.sciencedirect.com/science/article/pii/S1474442214702194en


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