title: UNC13A is a modifier of survival in amyotrophic lateral sclerosis.
abstract: 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.
authors: Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, 3584 CX, Utrecht, The Netherlands.
authors: Frank P
authors: FP
authors: Diekstra
authors: Paul W J
authors: PW
authors: van Vught
authors: Wouter
authors: W
authors: van Rheenen
authors: Max
authors: M
authors: Koppers
authors: R Jeroen
authors: RJ
authors: Pasterkamp
authors: Michael A
authors: MA
authors: van Es
authors: Helenius J
authors: HJ
authors: Schelhaas
authors: Marianne
authors: M
authors: de Visser
authors: Wim
authors: W
authors: Robberecht
authors: Philip
authors: P
authors: Van Damme
authors: Peter M
authors: PM
authors: Andersen
authors: Leonard H
authors: LH
authors: van den Berg
authors: Jan H
authors: JH
authors: Veldink
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000401:mortality*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000502:physiology*; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D009419:Nerve Tissue Proteins; C485548:UNC13B protein, human