title: Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis.
abstract: OBJECTIVE
  Several studies have suggested an increased frequency of variants in the gene encoding angiogenin (ANG) in patients with amyotrophic lateral sclerosis (ALS). Interestingly, a few ALS patients carrying ANG variants also showed signs of Parkinson disease (PD). Furthermore, relatives of ALS patients have an increased risk to develop PD, and the prevalence of concomitant motor neuron disease in PD is higher than expected based on chance occurrence. We therefore investigated whether ANG variants could predispose to both ALS and PD.
  
  
  METHODS
  We reviewed all previous studies on ANG in ALS and performed sequence experiments on additional samples, which allowed us to analyze data from 6,471 ALS patients and 7,668 controls from 15 centers (13 from Europe and 2 from the USA). We sequenced DNA samples from 3,146 PD patients from 6 centers (5 from Europe and 1 from the USA). Statistical analysis was performed using the variable threshold test, and the Mantel-Haenszel procedure was used to estimate odds ratios.
  
  
  RESULTS
  Analysis of sequence data from 17,258 individuals demonstrated a significantly higher frequency of ANG variants in both ALS and PD patients compared to control subjects (p = 9.3 × 10(-6) for ALS and p = 4.3 × 10(-5) for PD). The odds ratio for any ANG variant in patients versus controls was 9.2 for ALS and 6.7 for PD.
  
  
  CONCLUSIONS
  The data from this multicenter study demonstrate that there is a strong association between PD, ALS, and ANG variants. ANG is a genetic link between ALS and PD.
authors.affiliation: Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, The Netherlands.
authors.forename: Michael A
authors.initials: MA
authors.lastname: van Es
authors.forename: Helenius J
authors.initials: HJ
authors.lastname: Schelhaas
authors.forename: Paul W J
authors.initials: PW
authors.lastname: van Vught
authors.forename: Nicola
authors.initials: N
authors.lastname: Ticozzi
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authors.initials: PM
authors.lastname: Andersen
authors.forename: Ewout J N
authors.initials: EJ
authors.lastname: Groen
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authors.initials: C
authors.lastname: Schulte
authors.forename: Hylke M
authors.initials: HM
authors.lastname: Blauw
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authors.initials: M
authors.lastname: Koppers
authors.forename: Frank P
authors.initials: FP
authors.lastname: Diekstra
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authors.initials: K
authors.lastname: Fumoto
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authors.lastname: LeClerc
authors.forename: Pamela
authors.initials: P
authors.lastname: Keagle
authors.forename: Bastiaan R
authors.initials: BR
authors.lastname: Bloem
authors.forename: Hans
authors.initials: H
authors.lastname: Scheffer
authors.forename: Bart F L
authors.initials: BF
authors.lastname: van Nuenen
authors.forename: Marka
authors.initials: M
authors.lastname: van Blitterswijk
authors.forename: Wouter
authors.initials: W
authors.lastname: van Rheenen
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authors.initials: AM
authors.lastname: Wills
authors.forename: Patrick P
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authors.lastname: Lowe
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authors.lastname: Hu
authors.forename: Wenhao
authors.initials: W
authors.lastname: Yu
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kishikawa
authors.forename: David
authors.initials: D
authors.lastname: Wu
authors.forename: Rebecca D
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authors.lastname: Folkerth
authors.forename: Claudio
authors.initials: C
authors.lastname: Mariani
authors.forename: Stefano
authors.initials: S
authors.lastname: Goldwurm
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authors.initials: G
authors.lastname: Pezzoli
authors.forename: Philip
authors.initials: P
authors.lastname: Van Damme
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authors.initials: R
authors.lastname: Lemmens
authors.forename: Caroline
authors.initials: C
authors.lastname: Dahlberg
authors.forename: Anna
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authors.lastname: Birve
authors.forename: Rubén
authors.initials: R
authors.lastname: Fernández-Santiago
authors.forename: Stefan
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authors.lastname: Waibel
authors.forename: Christine
authors.initials: C
authors.lastname: Klein
authors.forename: Markus
authors.initials: M
authors.lastname: Weber
authors.forename: Anneke J
authors.initials: AJ
authors.lastname: van der Kooi
authors.forename: Marianne
authors.initials: M
authors.lastname: de Visser
authors.forename: Dagmar
authors.initials: D
authors.lastname: Verbaan
authors.forename: Jacobus J
authors.initials: JJ
authors.lastname: van Hilten
authors.forename: Peter
authors.initials: P
authors.lastname: Heutink
authors.forename: Eric A M
authors.initials: EA
authors.lastname: Hennekam
authors.forename: Edwin
authors.initials: E
authors.lastname: Cuppen
authors.forename: Daniela
authors.initials: D
authors.lastname: Berg
authors.forename: Robert H
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authors.lastname: Brown
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Silani
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authors.initials: T
authors.lastname: Gasser
authors.forename: Albert C
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authors.lastname: Ludolph
authors.forename: Wim
authors.initials: W
authors.lastname: Robberecht
authors.forename: Roel A
authors.initials: RA
authors.lastname: Ophoff
authors.forename: Jan H
authors.initials: JH
authors.lastname: Veldink
authors.forename: R Jeroen
authors.initials: RJ
authors.lastname: Pasterkamp
authors.forename: Paul I W
authors.initials: PI
authors.lastname: de Bakker
authors.forename: John E
authors.initials: JE
authors.lastname: Landers
authors.forename: Bart P
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authors.lastname: van de Warrenburg
authors.forename: Leonard H
authors.initials: LH
authors.lastname: van den Berg
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D016208:Databases, Factual / Q000706:statistics & numerical data; D005060:Europe; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008297:Male; D015337:Multicenter Studies as Topic; D010300:Parkinson Disease / Q000235:genetics*; D012259:Ribonuclease, Pancreatic / Q000235:genetics*; D014481:United States
chemical_list: C046366:angiogenin; D012259:Ribonuclease, Pancreatic