title: The emerging role of SMPD1 mutations in Parkinson's disease: Implications for future studies.
abstract: Recently, an additional study confirmed the association between SMPD1 mutations and Parkinson's disease (PD). While the first study on SMPD1 and PD suggested that only one SMPD1 mutations is responsible for the association to PD, the recent study argued that all SMPD1 mutations may be associated with an increased risk for PD. Since SMPD1 mutations are being routinely screened in some populations with high carrier frequencies, and since it will be further screened in additional PD populations, it is important to better define the association between SMPD1 and PD. We reanalyzed the data from the recent and previous papers, and we show that the association between SMPD1 and PD is indeed not driven by only one mutation, but it is also not driven by all SMPD1 mutations. In the Ashkenazi-Jewish population, the p.fs330P (OR = 3.03, p = 0.0026) and p.L302P (OR = 9.62, p < 0.0001) are associated with PD, and the p.R496L mutation is not (OR = 0.84, p = 0.71), and similar observation was noted in the Chinese population. Thus, we conclude that similar to the GBA gene where different mutations have differential effects, SMPD1 mutations also have a differential effects on the risk for PD. Future studies should therefore examine the association by mutation and not by accumulative risk of all mutations.
authors: Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada; The Department of Human Genetics, McGill University, Montreal, Quebec, Canada; The Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada. Electronic address: ziv.gan-or@mail.mcgill.ca.
authors: Ziv
authors: Z
authors: Gan-Or
authors: Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel; The Genetic Institute, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.
authors: Avi
authors: A
authors: Orr-Urtreger
authors: The Department of Neurology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors: Roy N
authors: RN
authors: Alcalay
authors: The Department of Neurology, Mount Sinai Beth Israel Medical Center, New York, NY, USA.
authors: Susan
authors: S
authors: Bressman
authors: Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel; The Department of Neurology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.
authors: Nir
authors: N
authors: Giladi
authors: Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada; The Department of Human Genetics, McGill University, Montreal, Quebec, Canada; The Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
authors: Guy A
authors: GA
authors: Rouleau
mesh_terms: D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics*; D013108:Sphingomyelin Phosphodiesterase / Q000235:genetics*
chemical_list: D013108:Sphingomyelin Phosphodiesterase
keywords: GBA; Genetics; Parkinson's disease; SMPD1