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Genome-wide identif...
Genome-wide identification of the genetic basis of amyotrophic lateral sclerosis
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- Zhang, Sai (author)
- Stanford University
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- Cooper-Knock, Johnathan (author)
- University of Sheffield
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- Weimer, Annika K (author)
- Stanford University
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- Shi, Minyi (author)
- Stanford University
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- Moll, Tobias (author)
- University of Sheffield
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- Marshall, Jack N G (author)
- University of Sheffield
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- Harvey, Calum (author)
- University of Sheffield
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- Nezhad, Helia Ghahremani (author)
- Sheffield Hallam University
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- Franklin, John (author)
- University of Sheffield
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- Souza, Cleide Dos Santos (author)
- University of Sheffield
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- Ning, Ke (author)
- University of Sheffield
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- Wang, Cheng (author)
- University of California, San Francisco
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- Li, Jingjing (author)
- University of California, San Francisco
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- Dilliott, Allison A (author)
- McGill University
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- Farhan, Sali (author)
- McGill University
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- Elhaik, Eran (author)
- Lund University,Lunds universitet,Molekylär cellbiologi,Biologiska institutionen,Naturvetenskapliga fakulteten,Bioinformatik,Forskargrupper vid Lunds universitet,Molecular Cell Biology,Department of Biology,Faculty of Science,Bioinformatics,Lund University Research Groups
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- Pasniceanu, Iris (author)
- University of Sheffield
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- Livesey, Matthew R (author)
- University of Sheffield
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- Eitan, Chen (author)
- Weizmann Institute of Science Israel
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- Hornstein, Eran (author)
- Weizmann Institute of Science Israel
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- Kenna, Kevin P (author)
- University Medical Center Utrecht
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- Veldink, Jan H (author)
- University Medical Center Utrecht
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- Ferraiuolo, Laura (author)
- University of Sheffield
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- Shaw, Pamela J (author)
- University of Sheffield
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- Snyder, Michael P (author)
- Stanford University
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(creator_code:org_t)
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- Elsevier BV, 2022
- 2022
- English.
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In: Neuron. - : Elsevier BV. - 0896-6273. ; 110:6, s. 11-1008
- Related links:
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http://dx.doi.org/10... (free)
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http://www.cell.com/...
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https://doi.org/10.1...
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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Neuron
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To the university's database
- By the author/editor
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Zhang, Sai
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Cooper-Knock, Jo ...
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Weimer, Annika K
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Shi, Minyi
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Moll, Tobias
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Marshall, Jack N ...
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show more...
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Harvey, Calum
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Nezhad, Helia Gh ...
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Franklin, John
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Souza, Cleide Do ...
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Ning, Ke
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Wang, Cheng
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Li, Jingjing
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Dilliott, Alliso ...
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Farhan, Sali
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Elhaik, Eran
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Pasniceanu, Iris
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Livesey, Matthew ...
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Eitan, Chen
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Hornstein, Eran
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Kenna, Kevin P
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Veldink, Jan H
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Ferraiuolo, Laur ...
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Shaw, Pamela J
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Snyder, Michael ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- Articles in the publication
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Neuron
- By the university
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Lund University