@article{Kenna2016, 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 = {Kenna, Kevin P. and van Doormaal, Perry T. C. and Dekker, Annelot M. and Ticozzi, Nicola and Kenna, Brendan J. and Diekstra, Frank P. and van Rheenen, Wouter and van Eijk, Kristel R. and Jones, Ashley R. and Keagle, Pamela and Shatunov, Aleksey and Sproviero, William and Smith, Bradley N. and van Es, Michael A. and Topp, Simon D. and Kenna, Aoife and Miller, Jack W. and Fallini, Claudia and Tiloca, Cinzia and Mclaughlin, Russell L. and Vance, Caroline and Troakes, Claire and Colombrita, Claudia and Mora, Gabriele and Calvo, Andrea and Verde, Federico and Al-Sarraj, Safa and King, Andrew and Calini, Daniela and de Belleroche, Jacqueline and Baas, Frank and van der Kooi, Anneke J. and de Visser, Marianne and Doormaal, Perry and ten Asbroek, Anneloor L. M. A. and Sapp, Peter C. and Ten Asbroek, Anneloor L. and McKenna-Yasek, Diane and Polak, Meraida and Asress, Seneshaw and Muñoz-Blanco, José Luis and Strom, Tim M. and Meitinger, Thomas and Morrison, Karen E. and D'Alfonso, Sandra and Mazzini, Letizia and Mazzin, i. L. and Del Bo, Roberto and Ceroni, Mauro and Comi, Gp and Gagliardi, Stella and Querin, Giorgia and Bertolin, Cinzia and Pensato, Viviana and Castellotti, Barbara and Corti, Stefania and Cereda, Cristina and Corrado, Lucia and Sorarù, Gianni and Lauria, Giuseppe 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. and Pall, Hardev and Shaw, Pamela J. and Turner, Martin R. and Talbot, Kevin and Taroni, Franco and Boylan, Kevin B. and Van Blitterswijk, Marka and Rademakers, Rosa and Esteban-Pérez, Jesús and García-Redondo, Alberto and Van Damme, Phillip and Robberecht, Wim and Chio, Adriano and Gellera, Cinzia and Drepper, Carsten and Sendtner, Michael and Ratti, Antonia and Glass, Jonathan D. and Mora, Jesús S. and Basak, Nazli A. and Hardiman, Orla and Ludolph, Albert C. and Andersen, Peter M. and Weishaupt, Jochen H. and Brown, Robert H. and Al-Chalabi, Ammar and Silani, Vincenzo and Shaw, Christopher E. and van den Berg, Leonard H. and Veldink, Jan H. and Landers, John E.}, doi = {10.1038/ng.3626}, journal = {Nature Genetics}, month = {jan}, pages = {1037-1042}, title = {NEK1 variants confer susceptibility to amyotrophic lateral sclerosis}, url = {http://eprints.whiterose.ac.uk/121408/1/nihms885013.pdf}, volume = {48}, year = {2016} }