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. INTERPRETATION: 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.
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. INTERPRETATION: 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: A B Singleton; M Farrer; J Johnson; A Singleton; S Hague; J Kachergus; M Hulihan; T Peuralinna; A Dutra; R Nussbaum; S Lincoln; A Crawley; M Hanson; D Maraganore; C Adler; M R Cookson; M Muenter; M Baptista; D Miller; J Blancato; J Hardy; K Gwinn-Hardy Journal: Science Date: 2003-10-31 Impact factor: 47.728
Authors: E Sidransky; M A Nalls; J O Aasly; J Aharon-Peretz; G Annesi; E R Barbosa; A Bar-Shira; D Berg; J Bras; A Brice; C-M Chen; L N Clark; C Condroyer; E V De Marco; A Dürr; M J Eblan; S Fahn; M J Farrer; H-C Fung; Z Gan-Or; T Gasser; R Gershoni-Baruch; N Giladi; A Griffith; T Gurevich; C Januario; P Kropp; A E Lang; G-J Lee-Chen; S Lesage; K Marder; I F Mata; A Mirelman; J Mitsui; I Mizuta; G Nicoletti; C Oliveira; R Ottman; A Orr-Urtreger; L V Pereira; A Quattrone; E Rogaeva; A Rolfs; H Rosenbaum; R Rozenberg; A Samii; T Samaddar; C Schulte; M Sharma; A Singleton; M Spitz; E-K Tan; N Tayebi; T Toda; A R Troiano; S Tsuji; M Wittstock; T G Wolfsberg; Y-R Wu; C P Zabetian; Y Zhao; S G Ziegler Journal: N Engl J Med Date: 2009-10-22 Impact factor: 91.245
Authors: Sonja W Scholz; Henry Houlden; Claudia Schulte; Manu Sharma; Abi Li; Daniela Berg; Anna Melchers; Reema Paudel; J Raphael Gibbs; Javier Simon-Sanchez; Coro Paisan-Ruiz; Jose Bras; Jinhui Ding; Honglei Chen; Bryan J Traynor; Sampath Arepalli; Ryan R Zonozi; Tamas Revesz; Janice Holton; Nick Wood; Andrew Lees; Wolfgang Oertel; Ullrich Wüllner; Stefano Goldwurm; Maria Teresa Pellecchia; Thomas Illig; Olaf Riess; Hubert H Fernandez; Ramon L Rodriguez; Michael S Okun; Werner Poewe; Gregor K Wenning; John A Hardy; Andrew B Singleton; Francesca Del Sorbo; Susanne Schneider; Kailash P Bhatia; Thomas Gasser Journal: Ann Neurol Date: 2009-05 Impact factor: 10.422
Authors: Colleen M Dewey; Basar Cenik; Chantelle F Sephton; Brett A Johnson; Joachim Herz; Gang Yu Journal: Brain Res Date: 2012-02-22 Impact factor: 3.252