An investigation of replicated genetic associations from a genome-wide study of sporadic MND.

Lead Research Organisation: King's College London
Department Name: Neurology

Abstract

We are trying to find genes that make people likely to develop motor neuron disease (MND). This is a wasting disease in which an affected person becomes progressively paralysed over months until they are too weak to breathe.
We know that a few people with MND carry a genetic mutation. For most people with MND we think that certain common genetic variations might increase the risk in certain situations.
MND takes many forms and we do not know if they are really all the same underlying disease or several different conditions that happen to look the same. This makes gene-hunting difficult. Also, even though MND is quite common (about 1 in every 400 people will die from it), life expectancy is very poor and so at any one time there are not many affected people who can help with research.
We have successfully found a genetic signal for MND on chromosome 8 but we now need to pinpoint where the signal is coming from. If we can find out exactly what genetic variation in this area is responsible, we will understand more about MND and this will make it easier to develop a treatment.

Technical Summary

Background:
Motor Neuron Disease (MND) is a fatal adult-onset neurological disorder that causes progressive muscle weakness gradually affecting the power of speech, swallowing and limb movement. There is significant disability from the outset and eventually patients are left immobile, unable to communicate or care for themselves. Relentless disease progression engenders feelings of hopelessness so that some people travel abroad seeking euthanasia. The only drug shown to impact on survival, riluzole, has only a modest effect in slowing disease progression and treatment is otherwise largely symptomatic. The mean age of onset is between 50-60 years, cutting short the productive lives of many individuals. Death from respiratory failure usually occurs within 3 years of symptom onset and only 4% of patients survive more than 10 years. Although it is commonly thought of as a rare disease, the lifetime risk is about 1 in 400, with 1 in 380 death certificates carrying this diagnosis in the UK, and since the risk increases with age, it will become more common as the population ages. At present the diagnosis of MND is a death sentence with a miserable disease course, making it one of the most feared illnesses in the developed world.
Previous findings:
In an MRC-funded study, we have performed a genome-wide association study using 300 case and 300 control samples and 2,336 microsatellite markers. The markers were targeted at both gene-dense regions using a method we developed, and at regions previously shown to be of interest in MND. A DNA pooling strategy was followed by individual genotyping of markers of interest. Of the markers analysed, all showed confirmed association in individuals, and one on chromosome 8 showed replicated association in two other populations, from Belgium and the USA.
Objective:
To identify the functional variant(s) associated with sporadic motor neuron disease in the region we have identified on chromosome 8
Methods:
We will analyse the MND-associated region with an informative set of tag-SNPs in UK samples, and fine-map the disease associated locus. We will identify the association peak and identify the strongest positional candidate genes and their functional variants. We will confirm the mapping in Belgian and US populations. This will allow us to examine functional effects of gene variants identified in the laboratory. In parallel with this, we will perform bioinformatics analysis of relevant DNA and protein sequences and expression studies of genotyped brains for secondary evidence (genomic convergence).

Publications

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Gaastra B (2016) Rare genetic variation in UNC13A may modify survival in amyotrophic lateral sclerosis. in Amyotrophic lateral sclerosis & frontotemporal degeneration

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Crockford CJ (2018) ECAS A-B-C: alternate forms of the Edinburgh Cognitive and Behavioural ALS Screen. in Amyotrophic lateral sclerosis & frontotemporal degeneration

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Jones AR (2014) Health utility decreases with increasing clinical stage in amyotrophic lateral sclerosis. in Amyotrophic lateral sclerosis & frontotemporal degeneration

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Wallace VC (2014) The evaluation of pain in amyotrophic lateral sclerosis: a case controlled observational study. in Amyotrophic lateral sclerosis & frontotemporal degeneration

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Keren N (2014) Evidence of an environmental effect on survival in ALS. in Amyotrophic lateral sclerosis & frontotemporal degeneration

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Van Der Spek RA (2018) Reconsidering the causality of TIA1 mutations in ALS. in Amyotrophic lateral sclerosis & frontotemporal degeneration

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Martin S (2017) The benefit of evolving multidisciplinary care in ALS: a diagnostic cohort survival comparison. in Amyotrophic lateral sclerosis & frontotemporal degeneration

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Balendra R (2014) Estimating clinical stage of amyotrophic lateral sclerosis from the ALS Functional Rating Scale. in Amyotrophic lateral sclerosis & frontotemporal degeneration

 
Title YouTube educational video on ALS 
Description Educational video on ALS research available on YouTube 
Type Of Art Film/Video/Animation 
Year Produced 2018 
Impact Patient information and understanding about ALS and research 
URL https://www.youtube.com/watch?v=7KVSbwe7bHo
 
Description Association of British Neurologists Genetics Advisory Committee
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
 
Description Contributor and editor of laboratory manual on complex disease genetics
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
 
Description ALS Therapy Project Grant (GWAS in ALS)
Amount £147,613 (GBP)
Organisation ALS Therapy Alliance 
Sector Charity/Non Profit
Country United States
Start 04/2009 
End 03/2013
 
Description ALSA Funder-initiated project grant (ALSOD website and database)/ALS Association
Amount £40,000 (GBP)
Organisation ALS Association 
Sector Charity/Non Profit
Country United States
Start 02/2010 
End 02/2011
 
Description Angel Fund, Project Grant (GWAS in ALS)
Amount £71,912 (GBP)
Organisation Angel Fund 
Sector Charity/Non Profit
Country Unknown
Start 01/2009 
End 12/2009
 
Description JPND STRENGTH
Amount £530,723 (GBP)
Funding ID MR/L501529/1 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 04/2014 
End 01/2017
 
Description MNDA Project Grant (ELP3 in ALS)
Amount £102,000 (GBP)
Organisation Motor Neurone Disease Association (MND) 
Sector Charity/Non Profit
Country United Kingdom
Start 05/2009 
End 04/2012
 
Description MNDA Project Grant (KIFAP3 in ALS)
Amount £200,000 (GBP)
Organisation Motor Neurone Disease Association (MND) 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2010 
End 11/2014
 
Description MRC DTA Studentship (The transcriptome in ALS)
Amount £48,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 10/2010 
End 09/2013
 
Description MRC Strategic Grant (Next generation gene hunting in ALS - coapplicant)
Amount £520,688 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 03/2010 
End 03/2011
 
Description Programme Grant (MIROCALS)
Amount £387,723 (GBP)
Funding ID 633413 
Organisation European Commission 
Department Horizon 2020
Sector Public
Country European Union (EU)
Start 09/2015 
End 08/2019
 
Description Research Grant (ALSoD)
Amount £40,000 (GBP)
Organisation Motor Neurone Disease Association (MND) 
Sector Charity/Non Profit
Country United Kingdom
Start 02/2017 
End 01/2020
 
Description Research Grant (ALSoD)
Amount £102,469 (GBP)
Organisation ALS Association 
Sector Charity/Non Profit
Country United States
Start 02/2017 
End 01/2020
 
Description Research Grant (ATXN2 penetrance)
Amount £134,207 (GBP)
Organisation Motor Neurone Disease Association (MND) 
Sector Charity/Non Profit
Country United Kingdom
Start 11/2015 
End 08/2019
 
Description Research Grant (Bioinformatics)
Amount £171,749 (GBP)
Organisation Motor Neurone Disease Association (MND) 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2014 
End 09/2017
 
Description Research Grant (HERV-K)
Amount £241,949 (GBP)
Organisation ALS Association 
Sector Charity/Non Profit
Country United States
Start 11/2017 
End 10/2019
 
Description Research Grant (JPND BRAIN-MEND)
Amount £2,044,052 (GBP)
Funding ID MR/R024804/1 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 02/2018 
End 01/2021
 
Description Research Grant Fellowship
Amount £265,000 (GBP)
Organisation Motor Neurone Disease Association (MND) 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2016 
End 02/2019
 
Title ALSOD 
Description An online resource for genetic studies of ALS with research tools and links to bioinformatics resources at http://alsod.iop.kcl.ac.uk 
Type Of Material Technology assay or reagent 
Year Produced 2008 
Provided To Others? Yes  
Impact Website is visited 9000 times a month on average. 
URL http://alsod.iop.kcl.ac.uk
 
Title GWAS data 
Description Genotypes from ALS patients and controls 
Type Of Material Biological samples 
Year Produced 2008 
Provided To Others? Yes  
Impact Discovery and reporting of new genes and loci for ALS. Discovery of a locus on chromosome 9 associated with ALS. This directly led to the identification of the C9orf72 gene expansion mutation in ALS, which is the commonest cause of ALS (about 10% in the UK). 
 
Title Project MinE databrowser 
Description Summary statistics and output from the Project MinE whole genome sequencing consortium 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? Yes  
Impact Increased ability for researchers to identify ALS genes or interpret their own findings. Increased collaboration. 
URL http://databrowser.projectmine.com/
 
Description ELP3_collaboration 
Organisation Harvard University
Country United States 
Sector Academic/University 
PI Contribution Lead for genetic and other analysis, overall strategy, and research direction.
Collaborator Contribution Development of a zebrafish model of ELP3. Introduction to another group working on fly models. Contribution of human samples.Contribution of human samples. Intellectual support.Contribution of human samplesIntellectual contributionStatistical support and adviceIntellectual contribution
Impact 18996918
Start Year 2008
 
Description ELP3_collaboration 
Organisation Howard Hughes Medical Institute
Country United States 
Sector Charity/Non Profit 
PI Contribution Lead for genetic and other analysis, overall strategy, and research direction.
Collaborator Contribution Development of a zebrafish model of ELP3. Introduction to another group working on fly models. Contribution of human samples.Contribution of human samples. Intellectual support.Contribution of human samplesIntellectual contributionStatistical support and adviceIntellectual contribution
Impact 18996918
Start Year 2008
 
Description ELP3_collaboration 
Organisation Massachusetts General Hospital
Country United States 
Sector Hospitals 
PI Contribution Lead for genetic and other analysis, overall strategy, and research direction.
Collaborator Contribution Development of a zebrafish model of ELP3. Introduction to another group working on fly models. Contribution of human samples.Contribution of human samples. Intellectual support.Contribution of human samplesIntellectual contributionStatistical support and adviceIntellectual contribution
Impact 18996918
Start Year 2008
 
Description ELP3_collaboration 
Organisation University of Hong Kong
Country Hong Kong 
Sector Academic/University 
PI Contribution Lead for genetic and other analysis, overall strategy, and research direction.
Collaborator Contribution Development of a zebrafish model of ELP3. Introduction to another group working on fly models. Contribution of human samples.Contribution of human samples. Intellectual support.Contribution of human samplesIntellectual contributionStatistical support and adviceIntellectual contribution
Impact 18996918
Start Year 2008
 
Description ELP3_collaboration 
Organisation University of Leuven
Department VIB Vesalius Research Center
Country Belgium 
Sector Academic/University 
PI Contribution Lead for genetic and other analysis, overall strategy, and research direction.
Collaborator Contribution Development of a zebrafish model of ELP3. Introduction to another group working on fly models. Contribution of human samples.Contribution of human samples. Intellectual support.Contribution of human samplesIntellectual contributionStatistical support and adviceIntellectual contribution
Impact 18996918
Start Year 2008
 
Description ELP3_collaboration 
Organisation Utrecht University
Department Rudolf Magnus Institute
Country Netherlands 
Sector Academic/University 
PI Contribution Lead for genetic and other analysis, overall strategy, and research direction.
Collaborator Contribution Development of a zebrafish model of ELP3. Introduction to another group working on fly models. Contribution of human samples.Contribution of human samples. Intellectual support.Contribution of human samplesIntellectual contributionStatistical support and adviceIntellectual contribution
Impact 18996918
Start Year 2008
 
Description EuroMOTOR 
Organisation European Commission
Department Seventh Framework Programme (FP7)
Country European Union (EU) 
Sector Public 
PI Contribution This is an EU FP7 collaboration that has been awarded funding. We are contributing to the genomics work package.
Collaborator Contribution Project start was February 2011. Partners have contributed genotype data, DNA, phenotype data and epidemiology data.
Impact 1. Aggregation of neurologic and neuropsychiatric disease in ALS kindreds: A population based case controlled cohort study of Familial and Sporadic ALS. Byrne S, Heverin M, Elamin M, Bede P, Lynch C, Kenna K, Maclaughlin R, Walsh C, Al Chalabi A, Hardiman O. Ann Neurol. 2013 Jul 9. doi: 10.1002/ana.23969. [Epub ahead of print] PMID: 23836460 [PubMed - as supplied by publisher] Related citations 2. Credibility analysis of putative disease-causing genes using bioinformatics. Abel O, Powell JF, Andersen PM, Al-Chalabi A. PLoS One. 2013 Jun 5;8(6):e64899. doi: 10.1371/journal.pone.0064899. Print 2013. PMID: 23755159 [PubMed - in process] Free PMC Article Related citations 3. Homozygosity analysis in amyotrophic lateral sclerosis. Mok K, Laaksovirta H, Tienari PJ, Peuralinna T, Myllykangas L, Chiò A, Traynor BJ, Nalls MA, Gurunlian N, Shatunov A, Restagno G, Mora G, Nigel Leigh P, Shaw CE, Morrison KE, Shaw PJ, Al-Chalabi A, Hardy J, Orrell RW. Eur J Hum Genet. 2013 Apr 24. doi: 10.1038/ejhg.2013.59. [Epub ahead of print] PMID: 23612577 [PubMed - as supplied by publisher] Related citations 4. Residual association at C9orf72 suggests an alternative amyotrophic lateral sclerosis-causing hexanucleotide repeat. Jones AR, Woollacott I, Shatunov A, Cooper-Knock J, Buchman V, Sproviero W, Smith B, Scott KM, Balendra R, Abel O, McGuffin P, Ellis CM, Shaw PJ, Morrison KE, Farmer A, Lewis CM, Leigh PN, Shaw CE, Powell JF, Al-Chalabi A. Neurobiol Aging. 2013 Sep;34(9):2234.e1-7. doi: 10.1016/j.neurobiolaging.2013.03.003. Epub 2013 Apr 12. PMID: 23587638 [PubMed - in process] Related citations 5. H63D polymorphism in HFE is not associated with amyotrophic lateral sclerosis. van Rheenen W, Diekstra FP, van Doormaal PT, Seelen M, Kenna K, McLaughlin R, Shatunov A, Czell D, van Es MA, van Vught PW, van Damme P, Smith BN, Waibel S, Schelhaas HJ, van der Kooi AJ, de Visser M, Weber M, Robberecht W, Hardiman O, Shaw PJ, Shaw CE, Morrison KE, Al-Chalabi A, Andersen PM, Ludolph AC, Veldink JH, van den Berg LH. Neurobiol Aging. 2013 May;34(5):1517.e5-7. doi: 10.1016/j.neurobiolaging.2012.07.020. Epub 2012 Oct 11. PMID: 23063643 [PubMed - indexed for MEDLINE] Related citations 6. Is language impairment more common than executive dysfunction in amyotrophic lateral sclerosis? Taylor LJ, Brown RG, Tsermentseli S, Al-Chalabi A, Shaw CE, Ellis CM, Leigh PN, Goldstein LH. J Neurol Neurosurg Psychiatry. 2013 May;84(5):494-8. doi: 10.1136/jnnp-2012-303526. Epub 2012 Oct 2. PMID: 23033353 [PubMed - indexed for MEDLINE] Related citations 7. Age of onset of amyotrophic lateral sclerosis is modulated by a locus on 1p34.1. ALSGEN Consortium, Ahmeti KB, Ajroud-Driss S, Al-Chalabi A, Andersen PM, Armstrong J, Birve A, Blauw HM, Brown RH, Bruijn L, Chen W, Chio A, Comeau MC, Cronin S, Diekstra FP, Soraya Gkazi A, Glass JD, Grab JD, Groen EJ, Haines JL, Hardiman O, Heller S, Huang J, Hung WY; ITALSGEN consortium, Jaworski JM, Jones A, Khan H, Landers JE, Langefeld CD, Leigh PN, Marion MC, McLaughlin RL, Meininger V, Melki J, Miller JW, Mora G, Pericak-Vance MA, Rampersaud E, Robberecht W, Russell LP, Salachas F, Saris CG, Shatunov A, Shaw CE, Siddique N, Siddique T, Smith BN, Sufit R, Topp S, Traynor BJ, Vance C, van Damme P, van den Berg LH, van Es MA, van Vught PW, Veldink JH, Yang Y, Zheng JG. Neurobiol Aging. 2013 Jan;34(1):357.e7-19. doi: 10.1016/j.neurobiolaging.2012.07.017. Epub 2012 Sep 5. PMID: 22959728 [PubMed - indexed for MEDLINE] Related citations 8. EPHA4 is a disease modifier of amyotrophic lateral sclerosis in animal models and in humans. Van Hoecke A, Schoonaert L, Lemmens R, Timmers M, Staats KA, Laird AS, Peeters E, Philips T, Goris A, Dubois B, Andersen PM, Al-Chalabi A, Thijs V, Turnley AM, van Vught PW, Veldink JH, Hardiman O, Van Den Bosch L, Gonzalez-Perez P, Van Damme P, Brown RH Jr, van den Berg LH, Robberecht W. Nat Med. 2012 Sep;18(9):1418-22. PMID: 22922411 [PubMed - indexed for MEDLINE] Related citations 9. A proposed staging system for amyotrophic lateral sclerosis. Roche JC, Rojas-Garcia R, Scott KM, Scotton W, Ellis CE, Burman R, Wijesekera L, Turner MR, Leigh PN, Shaw CE, Al-Chalabi A. Brain. 2012 Mar;135(Pt 3):847-52. doi: 10.1093/brain/awr351. Epub 2012 Jan 23. PMID: 22271664 [PubMed - indexed for MEDLINE] Free PMC Article Related citations
Start Year 2010
 
Description Exome sequencing in motor neuron disease: bioinformatic analyses and biological validation of novel variants 
Organisation Motor Neurone Disease Association (MND)
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution ALS research excellence
Collaborator Contribution financial
Impact Publication of new ALS genes
Start Year 2015
 
Description From ALS exomes to Functional assays: turning candidates into confirmed genes 
Organisation Medical Research Council (MRC)
Department Medical Research Foundation
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution Scientific expertise on ALS pathogenesis
Collaborator Contribution financial support
Impact None yet as started 5 months ago
Start Year 2015
 
Description KIFAP3 consortium 
Organisation BMI The Beaumont Hospital
Country United Kingdom 
Sector Private 
PI Contribution Lead for project. Contribution of samples. Intellectual contribution.
Collaborator Contribution Contribution of samples. Intellectual contribution.Contribution of samples. Contribution of expertise in functional studies.Contribution of samples.Contribution of samples.Intellectual contributionContribution of samples.Intellectual contribution
Impact Publication: PMID 19451621
Start Year 2007
 
Description KIFAP3 consortium 
Organisation Catholic University of Louvain
Country Belgium 
Sector Academic/University 
PI Contribution Lead for project. Contribution of samples. Intellectual contribution.
Collaborator Contribution Contribution of samples. Intellectual contribution.Contribution of samples. Contribution of expertise in functional studies.Contribution of samples.Contribution of samples.Intellectual contributionContribution of samples.Intellectual contribution
Impact Publication: PMID 19451621
Start Year 2007
 
Description KIFAP3 consortium 
Organisation Harvard University
Country United States 
Sector Academic/University 
PI Contribution Lead for project. Contribution of samples. Intellectual contribution.
Collaborator Contribution Contribution of samples. Intellectual contribution.Contribution of samples. Contribution of expertise in functional studies.Contribution of samples.Contribution of samples.Intellectual contributionContribution of samples.Intellectual contribution
Impact Publication: PMID 19451621
Start Year 2007
 
Description KIFAP3 consortium 
Organisation Howard Hughes Medical Institute
Country United States 
Sector Charity/Non Profit 
PI Contribution Lead for project. Contribution of samples. Intellectual contribution.
Collaborator Contribution Contribution of samples. Intellectual contribution.Contribution of samples. Contribution of expertise in functional studies.Contribution of samples.Contribution of samples.Intellectual contributionContribution of samples.Intellectual contribution
Impact Publication: PMID 19451621
Start Year 2007
 
Description KIFAP3 consortium 
Organisation Massachusetts General Hospital
Country United States 
Sector Hospitals 
PI Contribution Lead for project. Contribution of samples. Intellectual contribution.
Collaborator Contribution Contribution of samples. Intellectual contribution.Contribution of samples. Contribution of expertise in functional studies.Contribution of samples.Contribution of samples.Intellectual contributionContribution of samples.Intellectual contribution
Impact Publication: PMID 19451621
Start Year 2007
 
Description KIFAP3 consortium 
Organisation University Medical Center Utrecht (UMC)
Country Netherlands 
Sector Academic/University 
PI Contribution Lead for project. Contribution of samples. Intellectual contribution.
Collaborator Contribution Contribution of samples. Intellectual contribution.Contribution of samples. Contribution of expertise in functional studies.Contribution of samples.Contribution of samples.Intellectual contributionContribution of samples.Intellectual contribution
Impact Publication: PMID 19451621
Start Year 2007
 
Description KIFAP3 consortium 
Organisation University Paris Sud
Department University of Évry Val-d'Essonne
Country France 
Sector Academic/University 
PI Contribution Lead for project. Contribution of samples. Intellectual contribution.
Collaborator Contribution Contribution of samples. Intellectual contribution.Contribution of samples. Contribution of expertise in functional studies.Contribution of samples.Contribution of samples.Intellectual contributionContribution of samples.Intellectual contribution
Impact Publication: PMID 19451621
Start Year 2007
 
Description STRENGTH 
Organisation Cantonal Hospital St. Gallen
Country Switzerland 
Sector Hospitals 
PI Contribution This is a JPND Consortium for which I am coordinator
Collaborator Contribution We provide genetics, statistical, bioinformatics, epigenetics, epidemiology and complex disease expertise.
Impact Please see form publications. The collaboration is multidisciplinary including genetics, epidemiology, epigenetics, statistics and bioinformatics
Start Year 2014
 
Description STRENGTH 
Organisation Catholic University of Louvain
Country Belgium 
Sector Academic/University 
PI Contribution This is a JPND Consortium for which I am coordinator
Collaborator Contribution We provide genetics, statistical, bioinformatics, epigenetics, epidemiology and complex disease expertise.
Impact Please see form publications. The collaboration is multidisciplinary including genetics, epidemiology, epigenetics, statistics and bioinformatics
Start Year 2014
 
Description STRENGTH 
Organisation Karolinska Institute
Country Sweden 
Sector Academic/University 
PI Contribution This is a JPND Consortium for which I am coordinator
Collaborator Contribution We provide genetics, statistical, bioinformatics, epigenetics, epidemiology and complex disease expertise.
Impact Please see form publications. The collaboration is multidisciplinary including genetics, epidemiology, epigenetics, statistics and bioinformatics
Start Year 2014
 
Description STRENGTH 
Organisation National Institute of Health and Medical Research (INSERM)
Department Nimes (INSERM)
Country France 
Sector Public 
PI Contribution This is a JPND Consortium for which I am coordinator
Collaborator Contribution We provide genetics, statistical, bioinformatics, epigenetics, epidemiology and complex disease expertise.
Impact Please see form publications. The collaboration is multidisciplinary including genetics, epidemiology, epigenetics, statistics and bioinformatics
Start Year 2014
 
Description STRENGTH 
Organisation Trinity College Dublin
Country Ireland 
Sector Academic/University 
PI Contribution This is a JPND Consortium for which I am coordinator
Collaborator Contribution We provide genetics, statistical, bioinformatics, epigenetics, epidemiology and complex disease expertise.
Impact Please see form publications. The collaboration is multidisciplinary including genetics, epidemiology, epigenetics, statistics and bioinformatics
Start Year 2014
 
Description STRENGTH 
Organisation University Medical Center Utrecht (UMC)
Country Netherlands 
Sector Academic/University 
PI Contribution This is a JPND Consortium for which I am coordinator
Collaborator Contribution We provide genetics, statistical, bioinformatics, epigenetics, epidemiology and complex disease expertise.
Impact Please see form publications. The collaboration is multidisciplinary including genetics, epidemiology, epigenetics, statistics and bioinformatics
Start Year 2014
 
Description STRENGTH 
Organisation University of Leuven
Department laboratory for cognitive neurology
PI Contribution This is a JPND Consortium for which I am coordinator
Collaborator Contribution We provide genetics, statistical, bioinformatics, epigenetics, epidemiology and complex disease expertise.
Impact Please see form publications. The collaboration is multidisciplinary including genetics, epidemiology, epigenetics, statistics and bioinformatics
Start Year 2014
 
Description STRENGTH 
Organisation University of Milan
Country Italy 
Sector Academic/University 
PI Contribution This is a JPND Consortium for which I am coordinator
Collaborator Contribution We provide genetics, statistical, bioinformatics, epigenetics, epidemiology and complex disease expertise.
Impact Please see form publications. The collaboration is multidisciplinary including genetics, epidemiology, epigenetics, statistics and bioinformatics
Start Year 2014
 
Description STRENGTH 
Organisation University of Sheffield
Department Sheffield Institute for Translational Neuroscience (SITraN)
Country United Kingdom 
Sector Academic/University 
PI Contribution This is a JPND Consortium for which I am coordinator
Collaborator Contribution We provide genetics, statistical, bioinformatics, epigenetics, epidemiology and complex disease expertise.
Impact Please see form publications. The collaboration is multidisciplinary including genetics, epidemiology, epigenetics, statistics and bioinformatics
Start Year 2014
 
Description STRENGTH 
Organisation University of Turin
Country Italy 
Sector Academic/University 
PI Contribution This is a JPND Consortium for which I am coordinator
Collaborator Contribution We provide genetics, statistical, bioinformatics, epigenetics, epidemiology and complex disease expertise.
Impact Please see form publications. The collaboration is multidisciplinary including genetics, epidemiology, epigenetics, statistics and bioinformatics
Start Year 2014
 
Description STRENGTH 
Organisation University of Ulm
Country Germany 
Sector Academic/University 
PI Contribution This is a JPND Consortium for which I am coordinator
Collaborator Contribution We provide genetics, statistical, bioinformatics, epigenetics, epidemiology and complex disease expertise.
Impact Please see form publications. The collaboration is multidisciplinary including genetics, epidemiology, epigenetics, statistics and bioinformatics
Start Year 2014
 
Title Lithium PRELUDE trial 
Description We have shown that Lithium carbonate, while ineffective in ALS as a whole, is effective in people with a poor prognosis genetic variant in the UNC13A gene (homozygosity for the CC genotype). We are now seeking funding for a trial of lithium in patients with ALS who carry this poor prognosis variant. This will be a precision medicine approach in ALS. 
Type Therapeutic Intervention - Drug
Current Stage Of Development Initial development
Year Development Stage Completed 2019
Development Status Actively seeking support
Impact The initial findings have been published, and if the trial confirms the analysis, this will become a new treatment for ALS. 
URL https://www.ncbi.nlm.nih.gov/pubmed/28978660
 
Title ALSgenScanner 
Description ALSgeneScanner is a tool to allow neurologists to analyze whole genome sequence data for mutations specific to ALS and generates a detailed annotated report for each patient. 
Type Of Technology Software 
Year Produced 2019 
Open Source License? Yes  
Impact It has only just been released, but has had a good reception on social media platforms (Twitter in particular). 
URL https://www.tandfonline.com/doi/full/10.1080/21678421.2018.1562553
 
Title DNAscan 
Description A fast, computationally and memory efficient bioinformatics pipeline for the analysis of DNA next-generation-sequencing data 
Type Of Technology Software 
Year Produced 2018 
Open Source License? Yes  
Impact Improved analysis pipeline for the international Project MinE whole genome sequencing consortium (http://www.projectmine.com) 
URL https://www.biorxiv.org/content/early/2018/02/18/267195
 
Description Ask the Experts Panel at International Symposium 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Patients, carers and/or patient groups
Results and Impact A live audience and online audience watched a presentation and then asked questions on ALS research
Year(s) Of Engagement Activity 2015
URL https://www.youtube.com/watch?v=U98WU4Zzu8s
 
Description Broadcast news items on new gene discoveries 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Interviews with BBC World (live TV interview), ITV News (recorded TV), Channel 5 News (recorded TV), BBC Radio London (live radio) and others. Example URL below
Year(s) Of Engagement Activity 2015,2016
URL https://twitter.com/ammaralchalabi/status/758321315698933760
 
Description Edmond J Safra Memorial Lecture 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Presentation of research findings to a lay audience of key "high value" individuals, aiming to educate and improve philanthropic investment in research.

None known
Year(s) Of Engagement Activity 2009
 
Description General research dissemination videos on YouTube 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Multiple videos on YouTube, responding to interviews on ALS research
Year(s) Of Engagement Activity 2014,2015,2016
URL https://www.youtube.com/results?search_query=ammar+al-chalabi+als
 
Description JNNP Podcast 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I was interviewed for a podcast about our recent finding that genetic variants that increase ALS risk, also lower the age of onset. Our paper was Editor's Choice.
Year(s) Of Engagement Activity 2019
 
Description MNDA Legacy Event September 2018 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Supporters
Results and Impact The event was to educate the general public and those engaged with the MND Association about the research done that is funded by the MNDA, with the aim of increasing knowledge and encouraging a legacy to such research,
Year(s) Of Engagement Activity 2018
 
Description MNDA Legacy Event at King's College London 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact Between 40 and 70 people attended each event, consisting of research presentations, a tour of the labs, and an Ask the Experts session. The events were to raise awareness of our research, to improve donations to the patient organisation (MNDA), and to improve public understanding of our clinical and research programme. Increased donations have been reported, and feedback shows a high demand for future events.
Year(s) Of Engagement Activity 2017,2018
 
Description MNDA Newsletter 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Participants in your research and patient groups
Results and Impact A report on our research group activities for the MNDA newsletter

None evaluated
Year(s) Of Engagement Activity 2008,2009,2013,2014
 
Description MNDA information video on our research 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact A YouTube video posted also on the Motor Neurone Disease Association website, describing our research.
Year(s) Of Engagement Activity 2016
URL https://youtu.be/tKz81aFVB04
 
Description MNDA-sponsored VIP visit 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Participants in your research and patient groups
Results and Impact Hosted a visit to our labs by key people identified by the Motor Neurone Disease Association

Increased funding to the MNDA. Report from the MNDA describing increased funds as a direct result.
Year(s) Of Engagement Activity 2009,2012,2013,2014
 
Description Newspaper articles 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Interviewed by reporters with story on BBC website and others

None evaluated
Year(s) Of Engagement Activity 2009
 
Description Public lecture 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Public lecture on the genetics and biology of motor neuron disease
Year(s) Of Engagement Activity 2016
 
Description Public lecture on motor neuron disease research 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Supporters
Results and Impact I spoke at a dinner hosted by the MND Association for major donors at the Royal Institution
Year(s) Of Engagement Activity 2016