@article{942bf99909724be4819f5c8112fe04e9,
title = "NEK1 variants confer susceptibility to amyotrophic lateral sclerosis",
abstract = "To identify genetic factors contributing to amyotrophic lateral sclerosis (ALS), we conducted whole-exome analyses of 1,022 index familial ALS (FALS) cases and 7,315 controls. In a new screening strategy, we performed gene-burden analyses trained with established ALS genes and identified a significant association between loss-of-function (LOF) NEK1 variants and FALS risk. Independently, autozygosity mapping for an isolated community in the Netherlands identified a NEK1 p.Arg261His variant as a candidate risk factor. Replication analyses of sporadic ALS (SALS) cases and independent control cohorts confirmed significant disease association for both p.Arg261His (10,589 samples analyzed) and NEK1 LOF variants (3,362 samples analyzed). In total, we observed NEK1 risk variants in nearly 3% of ALS cases. NEK1 has been linked to several cellular functions, including cilia formation, DNA-damage response, microtubule stability, neuronal morphology and axonal polarity. Our results provide new and important insights into ALS etiopathogenesis and genetic etiology",
author = "{AUTHOR GROUP} and Kenna, {Kevin P.} and {van Doormaal}, {Perry T. C.} and Dekker, {Annelot M.} and Nicola Ticozzi and Kenna, {Brendan J.} and Diekstra, {Frank P.} and {van Rheenen}, Wouter and {van Eijk}, {Kristel R.} and Jones, {Ashley R.} and Pamela Keagle and Aleksey Shatunov and William Sproviero and Smith, {Bradley N.} and {van Es}, {Michael A.} and Topp, {Simon D.} and Aoife Kenna and Miller, {Jack W.} and Claudia Fallini and Cinzia Tiloca and McLaughlin, {Russell L.} and Caroline Vance and Claire Troakes and Claudia Colombrita and Gabriele Mora and Andrea Calvo and Federico Verde and Safa Al-Sarraj and Andrew King and Daniela Calini and {de Belleroche}, Jacqueline and Frank Baas and {van der Kooi}, {Anneke J.} and {de Visser}, Marianne and {ten Asbroek}, {Anneloor L. M. A.} and Sapp, {Peter C.} and Diane McKenna-Yasek and Meraida Polak and Seneshaw Asress and Mu{\~n}oz-Blanco, {Jos{\'e} Luis} and Strom, {Tim M.} and Thomas Meitinger and Morrison, {Karen E.} and Giuseppe Lauria and Williams, {Kelly L.} and Leigh, {P. Nigel} and Nicholson, {Garth A.} and Blair, {Ian P.} and Leblond, {Claire S.} and Dion, {Patrick A.} and Rouleau, {Guy A.}",
year = "2016",
doi = "https://doi.org/10.1038/ng.3626",
language = "English",
volume = "48",
pages = "1037--1042",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "9",
}