2026-07-25T15:24:48Zhttps://repisalud.isciii.es/rest/oai/request
oai:repisalud.isciii.es:20.500.12105/159072025-05-30T11:18:04Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19617
Repisalud author Al Khleifat, Ahmad author Iacoangeli, Alfredo author van Vugt, Joke J F A author Bowles, Harry author Moisse, Matthieu author Zwamborn, Ramona A J author van der Spek, Rick A A author Shatunov, Aleksey author Cooper-Knock, Johnathan author Topp, Simon author Byrne, Ross author Gellera, Cinzia author López-Alonso, Victoria author Jones, Ashley R author Opie-Martin, Sarah author Vural, Atay author Campos, Yolanda author van Rheenen, Wouter author Kenna, Brendan author Van Eijk, Kristel R author Kenna, Kevin author Weber, Markus author Smith, Bradley author Fogh, Isabella author Silani, Vincenzo author Morrison, Karen E author Dobson, Richard author van Es, Michael A author McLaughlin, Russell L author Vourc'h, Patrick author Chio, Adriano author Corcia, Philippe author de Carvalho, Mamede author Gotkine, Marc author Panades, Monica P author Mora, Jesus S author Shaw, Pamela J author Landers, John E author Glass, Jonathan D author Shaw, Christopher E author Basak, Nazli author Hardiman, Orla author Robberecht, Wim author Van Damme, Philip author van den Berg, Leonard H author Veldink, Jan H author Al-Chalabi, Ammar funder Wellcome Trust funder Unión Europea. Comisión Europea. 7 Programa Marco funder Unión Europea. Comisión Europea. H2020 funder Unión Europea. Fondo Social Europeo (ESF/FSE) funder Research Foundation - Flanders funder Katholieke Universiteit Leuven (Bélgica) funder Science Foundation Ireland funder NIH - National Institute of Neurological Disorders and Stroke (NINDS) (Estados Unidos) funder Amyotrophic Lateral Sclerosis Association (Estados Unidos) 2023-04-27T08:52:15Z 2023-04-27T08:52:15Z 2022-01-28 NPJ Genom Med. 2022 Jan 28;7(1):8. 10.1038/s41525-021-00267-9 2056-7944 NPJ genomic medicine 35091648 http://hdl.handle.net/20.500.12105/15907 There is a strong genetic contribution to Amyotrophic lateral sclerosis (ALS) risk, with heritability estimates of up to 60%. Both Mendelian and small effect variants have been identified, but in common with other conditions, such variants only explain a little of the heritability. Genomic structural variation might account for some of this otherwise unexplained heritability. We therefore investigated association between structural variation in a set of 25 ALS genes, and ALS risk and phenotype. As expected, the repeat expansion in the C9orf72 gene was identified as associated with ALS. Two other ALS-associated structural variants were identified: inversion in the VCP gene and insertion in the ERBB4 gene. All three variants were associated both with increased risk of ALS and specific phenotypic patterns of disease expression. More than 70% of people with respiratory onset ALS harboured ERBB4 insertion compared with 25% of the general population, suggesting respiratory onset ALS may be a distinct genetic subtype. eng Genome sequences Amyotrophic lateral sclerosis (ALS) Structural variation analysis of 6,500 whole genome sequences in amyotrophic lateral sclerosis research article 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 URL https://repisalud.isciii.es/bitstreams/1ff810dc-feab-4be5-881a-f423759d15b1/download File MD5 6f2bcbdc45db365630b0426cc38c0392 1119031 application/pdf StructuralVariationAnalysisGenome_2022.pdf URL https://repisalud.isciii.es/bitstreams/3c6ab6ea-c7ae-4ca9-8025-7c0eb3b8dd70/download File MD5 e52591677a5755e7bba32258f6f99b7c 820201 application/pdf Supplementary1_StructuralVariationAnalysisGenome_2022.pdf URL https://repisalud.isciii.es/bitstreams/d5eba938-6fe9-4000-9f9d-bee933688e92/download File MD5 eab045d55111adf7e8b976acdd945943 74825 application/pdf Supplementary2_StructuralVariationAnalysisGenome_2022.pdf URL https://repisalud.isciii.es/bitstreams/363a132e-54f0-490c-906f-55294927d833/download File MD5 90eab3144bd621eb628277cecf613b08 56409 text/plain StructuralVariationAnalysisGenome_2022.pdf.txt URL https://repisalud.isciii.es/bitstreams/0399a2d6-93e6-4a66-b9fb-1869c6124966/download File MD5 585de92f2be7570ee97172aa1f47b415 15289 text/plain Supplementary1_StructuralVariationAnalysisGenome_2022.pdf.txt URL https://repisalud.isciii.es/bitstreams/728c60bc-1977-43ca-b398-dc9e958ff4b8/download File MD5 0be60e580ece306ec9b341797df24faf 8954 text/plain Supplementary2_StructuralVariationAnalysisGenome_2022.pdf.txt