TY - JOUR
T1 - UNC13A is a modifier of survival in amyotrophic lateral sclerosis
AU - Diekstra, Frank P.
AU - van Vught, Paul W.J.
AU - van Rheenen, Wouter
AU - Koppers, Max
AU - Pasterkamp, R. Jeroen
AU - van Es, Michael A.
AU - Schelhaas, Helenius J.
AU - de Visser, Marianne
AU - Robberecht, Wim
AU - Van Damme, Philip
AU - Andersen, Peter M.
AU - van den Berg, Leonard H.
AU - Veldink, Jan H.
PY - 2012
Y1 - 2012
N2 - A large genome-wide screen in patients with sporadic amyotrophic lateral sclerosis (ALS) showed that the common variant rs12608932 in gene UNC13A was associated with disease susceptibility. UNC13A regulates the release of neurotransmitters, including glutamate. Genetic risk factors that, in addition, modify survival, provide promising therapeutic targets in ALS, a disease whose etiology remains largely elusive. We examined whether UNC13A was associated with survival of ALS patients in a cohort of 450 sporadic ALS patients and 524 unaffected controls from a population-based study of ALS in The Netherlands. Additionally, survival data were collected from individuals of Dutch, Belgian, or Swedish descent (1767 cases, 1817 controls) who had participated in a previously published genome-wide association study of ALS. We related survival to rs12608932 genotype. In both cohorts, the minor allele of rs12608932 in UNC13A was not only associated with susceptibility but also with shorter survival of ALS patients. Our results further corroborate the role of UNC13A in ALS pathogenesis. © 2012 Elsevier Inc.
AB - A large genome-wide screen in patients with sporadic amyotrophic lateral sclerosis (ALS) showed that the common variant rs12608932 in gene UNC13A was associated with disease susceptibility. UNC13A regulates the release of neurotransmitters, including glutamate. Genetic risk factors that, in addition, modify survival, provide promising therapeutic targets in ALS, a disease whose etiology remains largely elusive. We examined whether UNC13A was associated with survival of ALS patients in a cohort of 450 sporadic ALS patients and 524 unaffected controls from a population-based study of ALS in The Netherlands. Additionally, survival data were collected from individuals of Dutch, Belgian, or Swedish descent (1767 cases, 1817 controls) who had participated in a previously published genome-wide association study of ALS. We related survival to rs12608932 genotype. In both cohorts, the minor allele of rs12608932 in UNC13A was not only associated with susceptibility but also with shorter survival of ALS patients. Our results further corroborate the role of UNC13A in ALS pathogenesis. © 2012 Elsevier Inc.
UR - http://www.scopus.com/inward/record.url?scp=84855795589&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.neurobiolaging.2011.10.029
DO - https://doi.org/10.1016/j.neurobiolaging.2011.10.029
M3 - Article
C2 - 22118904
SN - 0197-4580
VL - 33
SP - 630.e3-630.e8
JO - Neurobiology of aging
JF - Neurobiology of aging
IS - 3
ER -
