AUTHOR=Al Khleifat Ahmad , Iacoangeli Alfredo , Jones Ashley R. , van Vugt Joke J. F. A. , Moisse Matthieu , Shatunov Aleksey , Zwamborn Ramona A. J. , van der Spek Rick A. A. , Cooper-Knock Johnathan , Topp Simon , van Rheenen Wouter , Kenna Brendan , Van Eijk Kristel R. , Kenna Kevin , Byrne Ross , López Victoria , Opie-Martin Sarah , Vural Atay , Campos Yolanda , Weber Markus , Smith Bradley , Fogh Isabella , Silani Vincenzo , Morrison Karen E. , Dobson Richard , van Es Michael A. , McLaughlin Russell L. , Vourc’h Patrick , Chio Adriano , Corcia Philippe , de Carvalho Mamede , Gotkine Marc , Panades Monica Povedano , Mora Jesus S. , Shaw Pamela J. , Landers John E. , Glass Jonathan D. , Shaw Christopher E. , Basak Nazli , Hardiman Orla , Robberecht Wim , Van Damme Philip , van den Berg Leonard H. , Veldink Jan H. , Al-Chalabi Ammar 

TITLE=Telomere length analysis in amyotrophic lateral sclerosis using large-scale whole genome sequence data

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=Volume 16 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2022.1050596

DOI=10.3389/fncel.2022.1050596

ISSN=1662-5102

ABSTRACT=Amyotrophic lateral sclerosis (ALS), a neurodegenerative disease of motor neurons, is a complex genetic disease with heritability of 60%. Only about 14% of apparently sporadic ALS is explained by known genetic variation, suggesting that other forms of genetic variation are important, in addition to the known risk factors, male sex and increasing age. Telomeres maintain DNA integrity during cellular replication, differ between sexes, and shorten naturally with age. We find that longer telomeres are associated with ALS and specific phenotypic patterns of disease expression. We see the same pattern of telomere elongation in ALS in brain tissue. The association of longer telomeres with apparently sporadic ALS was also seen in people with familial ALS, supporting the notion that sporadic and familial ALS are not mutually exclusive categories but rather a spectrum.