TY - JOUR
T1 - Association of NIPA1 repeat expansions with amyotrophic lateral sclerosis in a large international cohort
AU - Tazelaar, Gij S. H. P.
AU - Dekker, Annelot M.
AU - van Vugt, Joke J. F. A.
AU - van der Spek, Rick A.
AU - Westeneng, Henk-Jan
AU - Kool, Lindy J. B. G.
AU - Kenna, Kevin P.
AU - van Rheenen, Wouter
AU - Pulit, Sara L.
AU - McLaughlin, Russell L.
AU - Sproviero, William
AU - Iacoangeli, Alfredo
AU - Huebers, Annemarie
AU - Brenner, David
AU - Morrison, Karen E.
AU - Shaw, Pamela J.
AU - Shaw, Christopher E.
AU - Povedano Panades, Monica
AU - Mora Pardina, Jesus S.
AU - Glass, Jonathan D.
AU - Hardiman, Orla
AU - Al-Chalabi, Ammar
AU - van Damme, Philip
AU - Robberecht, Wim
AU - Landers, John E.
AU - Ludolph, Albert C.
AU - Weishaupt, Jochen H.
AU - van den Berg, Leonard H.
AU - Veldink, Jan H.
AU - van Es, Michael A.
AU - Akcimen, Fulya
AU - Al Khleifat, Ahmad
AU - Andersen, Peter
AU - Basak, A. Nazli
AU - Bauer, Denis C.
AU - Blair, Ian
AU - Brands, William J.
AU - Byrne, Ross P.
AU - Calvo, Andrea
AU - Gonzalez, Yolanda Campos
AU - Chio, Adriano
AU - Cooper-Knock, Jonothan
AU - Corcia, Philippe
AU - Couratier, Philippe
AU - de Carvalho, Mamede
AU - Drory, Vivian E.
AU - Eitan, Chen
AU - Garcia Redondo, Alberto
AU - Gellera, Cinzia
AU - Hornstein, Eran
N1 - This study was supported by the ALS Foundation Netherlands, the Belgian ALS Liga and National Lottery, and Agency for Innovation by Science and Technology (IWT), and the MND Association (UK) (Project MinE, www.projectmine.com). Research leading to these results has received funding from the European Community's Health Seventh Framework Program (FP7/2007-2013). This study was supported by ZonMW under the frame of E-Rare-2, the ERA Net for Research on Rare Diseases (PYRAMID). This is an EU Joint Programme–Neurodegenerative Disease Research (JPND) project (STRENGTH, MEND, SOPHIA, ALS-CarE). The project is supported through the following funding organizations under the aegis of JPND: UK, Medical Research Council (MR/L501529/1; MR/R024804/1) and Economic and Social Research Council (ES/L008238/1); Ireland, Health Research Board; the Netherlands, ZonMw; Belgium, FWO-Vlaanderen. Samples used in this research were in part obtained from the UK National DNA Bank for MND Research, funded by the MND Association and the Wellcome Trust. This project was supported by the MND Association of England, Wales and Northern Ireland and the Netherlands Organisation for Health Research and Development (Vici scheme to L.H. van den Berg and veni scheme to M.A. van Es). NDAL cordially thanks Suna and Inan Kirac Foundation for their generous support. M.A. van Es is supported by the Thierry Latran Foundation, the Dutch ALS foundation and the Rudolf Magnus Brain Center Talent Fellowship. C.E. Shaw and A Al-Chalabi receive salary support from the National Institute for Health Research (NIHR) Dementia Biomedical Research Unit and Biomedical Research Center in Mental Health at South London and Maudsley NHS Foundation Trust and King's College London. O. Hardiman is funded by the Health Research Board Clinician Scientist Program and Science Foundation Ireland. J.E. Landers is supported by the US National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke (R01NS073873) and the American ALS Association. R.L. McLaughlin is supported by the Thierry Latran Foundation and the ALS Association (2284). P. Van Damme holds a senior clinical investigatorship from FWO-Vlaanderen.
PY - 2019/2/1
Y1 - 2019/2/1
N2 - NIPA1 (nonimprinted in Prader-Willi/Angelman syndrome 1) mutations are known to cause hereditary spastic paraplegia type 6, a neurodegenerative disease that phenotypically overlaps to some extent with amyotrophic lateral sclerosis (ALS). Previously, a genomewide screen for copy number variants found an association with rare deletions in NIPA1 and ALS, and subsequent genetic analyses revealed that long (or expanded) polyalanine repeats in NIPA1 convey increased ALS susceptibility. We set out to perform a large-scale replication study to further investigate the role of NIPA1 polyalanine expansions with ALS, in which we characterized NIPA1 repeat size in an independent international cohort of 3955 patients with ALS and 2276 unaffected controls and combined our results with previous reports. Meta-analysis on a total of 6245 patients with ALS and 5051 controls showed an overall increased risk of ALS in those with expanded (>8) GCG repeat length (odds ratio = 1.50, p = 3.8x10(-5)). Together with previous reports, these findings provide evidence for an association of an expanded polyalanine repeat in NIPA1 and ALS. (C) 2018 Elsevier Inc. All rights reserved.
AB - NIPA1 (nonimprinted in Prader-Willi/Angelman syndrome 1) mutations are known to cause hereditary spastic paraplegia type 6, a neurodegenerative disease that phenotypically overlaps to some extent with amyotrophic lateral sclerosis (ALS). Previously, a genomewide screen for copy number variants found an association with rare deletions in NIPA1 and ALS, and subsequent genetic analyses revealed that long (or expanded) polyalanine repeats in NIPA1 convey increased ALS susceptibility. We set out to perform a large-scale replication study to further investigate the role of NIPA1 polyalanine expansions with ALS, in which we characterized NIPA1 repeat size in an independent international cohort of 3955 patients with ALS and 2276 unaffected controls and combined our results with previous reports. Meta-analysis on a total of 6245 patients with ALS and 5051 controls showed an overall increased risk of ALS in those with expanded (>8) GCG repeat length (odds ratio = 1.50, p = 3.8x10(-5)). Together with previous reports, these findings provide evidence for an association of an expanded polyalanine repeat in NIPA1 and ALS. (C) 2018 Elsevier Inc. All rights reserved.
UR - http://www.scopus.com/inward/record.url?scp=85054853443&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2018.09.012
DO - 10.1016/j.neurobiolaging.2018.09.012
M3 - مقالة
SN - 0197-4580
VL - 74
SP - 234.e9-234.e15
JO - Neurobiology of Aging
JF - Neurobiology of Aging
ER -