2026-07-25T15:24:47Zhttps://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

00925njm 22002777a 4500 dc 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 author 2022-01-28 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. 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 Genome sequences Amyotrophic lateral sclerosis (ALS) Structural variation analysis of 6,500 whole genome sequences in amyotrophic lateral sclerosis