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.
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).
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).
Organisations
- King's College London, United Kingdom (Lead Research Organisation)
- Catholic University of Louvain, Belgium (Collaboration)
- University of Hong Kong, Hong Kong (Collaboration)
- University of Leuven (Collaboration)
- University of Ulm, Germany (Collaboration)
- Karolinska Institute, Sweden (Collaboration)
- Utrecht University (Collaboration)
- Cantonal Hospital St. Gallen (Collaboration)
- University Medical Centre Utrecht, Netherlands (Collaboration)
- Grants Admin Office (Collaboration)
- Medical Research Council (Collaboration)
- Harvard University (Collaboration)
- University of Paris South 11, France (Collaboration)
- Howard Hughes Medical Institute (Collaboration)
- National Institute of Health and Medical Research (INSERM) (Collaboration)
- Massachusetts General Hospital (Collaboration)
- University of Turin (Collaboration)
- University of Milan, Italy (Collaboration)
- University of Sheffield, United Kingdom (Collaboration)
- Motor Neurone Disease Association (MND) (Collaboration)
- European Commission, Belgium (Collaboration)
- BMI The Beaumont Hospital (Collaboration)
Publications

Akimoto C
(2014)
A blinded international study on the reliability of genetic testing for GGGGCC-repeat expansions in C9orf72 reveals marked differences in results among 14 laboratories.
in Journal of medical genetics

Landers JE
(2008)
A common haplotype within the PON1 promoter region is associated with sporadic ALS.
in Amyotrophic lateral sclerosis : official publication of the World Federation of Neurology Research Group on Motor Neuron Diseases

Morgan S
(2017)
A comprehensive analysis of rare genetic variation in amyotrophic lateral sclerosis in the UK.
in Brain : a journal of neurology

Morgan S
(2017)
A comprehensive analysis of rare genetic variation in amyotrophic lateral sclerosis in the UK.
in Brain : a journal of neurology

Fogh I
(2014)
A genome-wide association meta-analysis identifies a novel locus at 17q11.2 associated with sporadic amyotrophic lateral sclerosis.
in Human molecular genetics

Blauw HM
(2010)
A large genome scan for rare CNVs in amyotrophic lateral sclerosis.
in Human molecular genetics

Wills AM
(2009)
A large-scale international meta-analysis of paraoxonase gene polymorphisms in sporadic ALS.
in Neurology

Ahmeti KB
(2013)
Age of onset of amyotrophic lateral sclerosis is modulated by a locus on 1p34.1.
in Neurobiology of aging

De Majo M
(2018)
ALS-associated missense and nonsense TBK1 mutations can both cause loss of kinase function.
in Neurobiology of aging

Wroe R
(2008)
ALSOD: the Amyotrophic Lateral Sclerosis Online Database.
in Amyotrophic lateral sclerosis : official publication of the World Federation of Neurology Research Group on Motor Neuron Diseases
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 |