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DC Field | Value | Language |
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dc.contributor.author | Zhang, Sai | - |
dc.contributor.author | Cooper-Knock, Johnathan | - |
dc.contributor.author | Weimer, Annika K. | - |
dc.contributor.author | Shi, Minyi | - |
dc.contributor.author | Moll, Tobias | - |
dc.contributor.author | Marshall, Jack N.G. | - |
dc.contributor.author | Harvey, Calum | - |
dc.contributor.author | Ghahremani Nezhad, Helia | - |
dc.contributor.author | Franklin, John | - |
dc.contributor.author | Santos Souza, Cleide dos | - |
dc.contributor.author | Ning, Ke | - |
dc.contributor.author | Wang, Cheng | - |
dc.contributor.author | Li, Jingjing | - |
dc.contributor.author | Dilliott, Allison A. | - |
dc.contributor.author | Farhan, Sali | - |
dc.contributor.author | Elhaik, Eran | - |
dc.contributor.author | Pasniceanu, Iris | - |
dc.contributor.author | Livesey, Matthew R. | - |
dc.contributor.author | Eitan, Chen | - |
dc.contributor.author | Hornstein, Eran | - |
dc.contributor.author | Kenna, Kevin P. | - |
dc.contributor.author | Veldink, Jan H. | - |
dc.contributor.author | Ferraiuolo, Laura | - |
dc.contributor.author | Shaw, Pamela J. | - |
dc.contributor.author | Snyder, Michael P. | - |
dc.contributor.author | Cauchi, Ruben J. | - |
dc.date.accessioned | 2022-11-09T06:19:10Z | - |
dc.date.available | 2022-11-09T06:19:10Z | - |
dc.date.issued | 2022 | - |
dc.identifier.citation | Zhang, S., Cooper-Knock, J., Weimer, A. K., Shi, M., Moll, T., Marshall, J. N., ... & Snyder, M. P. (2022). Genome-wide identification of the genetic basis of amyotrophic lateral sclerosis. Neuron, 110(6), 992-1008. | en_GB |
dc.identifier.uri | https://www.um.edu.mt/library/oar/handle/123456789/103514 | - |
dc.description.abstract | Amyotrophic lateral sclerosis (ALS) is a complex disease that leads to motor neuron death. Despite heritability estimates of 52%, genome-wide association studies (GWASs) have discovered relatively few loci. We developed a machine learning approach called RefMap, which integrates functional genomics with GWAS summary statistics for gene discovery. With transcriptomic and epigenetic profiling of motor neurons derived from induced pluripotent stem cells (iPSCs), RefMap identified 690 ALS-associated genes that represent a 5-fold increase in recovered heritability. Extensive conservation, transcriptome, network, and rare variant analyses demonstrated the functional significance of candidate genes in healthy and diseased motor neurons and brain tissues. Genetic convergence between common and rare variation highlighted KANK1 as a new ALS gene. Reproducing KANK1 patient mutations in human neurons led to neurotoxicity and demonstrated that TDP-43 mislocalization, a hallmark pathology of ALS, is downstream of axonal dysfunction. RefMap can be readily applied to other complex diseases. | en_GB |
dc.language.iso | en | en_GB |
dc.publisher | Elsevier Inc. | en_GB |
dc.rights | info:eu-repo/semantics/openAccess | en_GB |
dc.subject | Amyotrophic lateral sclerosis -- Diagnosis | en_GB |
dc.subject | Nervous system -- Degeneration | en_GB |
dc.subject | Machine learning | en_GB |
dc.subject | Genetics | en_GB |
dc.subject | Genes | en_GB |
dc.subject | Epigenetics | en_GB |
dc.title | Genome-wide identification of the genetic basis of amyotrophic lateral sclerosis | en_GB |
dc.type | article | en_GB |
dc.rights.holder | The copyright of this work belongs to the author(s)/publisher. The rights of this work are as defined by the appropriate Copyright Legislation or as modified by any successive legislation. Users may access this work and can make use of the information contained in accordance with the Copyright Legislation provided that the author must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the prior permission of the copyright holder | en_GB |
dc.contributor.corpauthor | Project MinE ALS Sequencing Consortium | en_GB |
dc.description.reviewed | peer-reviewed | en_GB |
dc.identifier.doi | 10.1016/j.neuron.2021.12.019 | - |
dc.publication.title | Neuron | en_GB |
Appears in Collections: | Scholarly Works - FacM&SPB |
Files in This Item:
File | Description | Size | Format | |
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Genome_wide_identification_of_the_genetic_basis_of_amyotrophic_lateral_sclerosis.pdf | 3.85 MB | Adobe PDF | View/Open |
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