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Analysis of amyotrophic lateral sclerosis as a multistep process: a population-based modelling study.

https://arctichealth.org/en/permalink/ahliterature260423
Source
Lancet Neurol. 2014 Nov;13(11):1108-13
Publication Type
Article
Date
Nov-2014
Author
Ammar 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
Source
Lancet Neurol. 2014 Nov;13(11):1108-13
Date
Nov-2014
Language
English
Publication Type
Article
Keywords
Adult
Aged
Amyotrophic Lateral Sclerosis - diagnosis - epidemiology
Disease Progression
England - epidemiology
Female
Finland - epidemiology
Humans
Ireland - epidemiology
Italy - epidemiology
Linear Models
Male
Middle Aged
Models, Theoretical
Population Surveillance - methods
Registries - statistics & numerical data
Scotland - epidemiology
Abstract
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.
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.
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 r(2)=0·95, Ireland r(2)=0·99, Italy r(2)=0·95, the Netherlands r(2)=0·99, and Scotland r(2)=0·97; overall r(2)=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).
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.
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).
Notes
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Comment In: Lancet Neurol. 2014 Nov;13(11):1067-825300935
PubMed ID
25300936 View in PubMed
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Chromosome 9 ALS and FTD locus is probably derived from a single founder.

https://arctichealth.org/en/permalink/ahliterature131202
Source
Neurobiol Aging. 2012 Jan;33(1):209.e3-8
Publication Type
Article
Date
Jan-2012
Author
Kin Mok
Bryan J Traynor
Jennifer Schymick
Pentti J Tienari
Hannu Laaksovirta
Terhi Peuralinna
Liisa Myllykangas
Adriano Chiò
Aleksey Shatunov
Bradley F Boeve
Adam L Boxer
Mariely DeJesus-Hernandez
Ian R Mackenzie
Adrian Waite
Nigel Williams
Huw R Morris
Javier Simón-Sánchez
John C van Swieten
Peter Heutink
Gabriella Restagno
Gabriele Mora
Karen E Morrison
Pamela J Shaw
Pamela Sara Rollinson
Ammar Al-Chalabi
Rosa Rademakers
Stuart Pickering-Brown
Richard W Orrell
Michael A Nalls
John Hardy
Author Affiliation
Reta Lila Weston Research Laboratories, Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK.
Source
Neurobiol Aging. 2012 Jan;33(1):209.e3-8
Date
Jan-2012
Language
English
Publication Type
Article
Keywords
Amyotrophic Lateral Sclerosis - genetics
Chromosomes, Human, Pair 9 - genetics
Finland
Frontotemporal Dementia - genetics
Genetic Linkage
Genome-Wide Association Study
Haplotypes
Humans
Polymorphism, Single Nucleotide
Abstract
We and others have recently reported an association between amyotrophic lateral sclerosis (ALS) and single nucleotide polymorphisms on chromosome 9p21 in several populations. Here we show that the associated haplotype is the same in all populations and that several families previously shown to have genetic linkage to this region also share this haplotype. The most parsimonious explanation of these data are that there is a single founder for this form of disease.
Notes
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PubMed ID
21925771 View in PubMed
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