The emerging role of SMPD1 mutations in Parkinson's disease: Implications for future studies

Parkinsonism Relat Disord. 2015 Oct;21(10):1294-5. doi: 10.1016/j.parkreldis.2015.08.018. Epub 2015 Aug 20.


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.

Keywords: GBA; Genetics; Parkinson's disease; SMPD1.

Publication types

  • Letter
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Comment

MeSH terms

  • Female
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Male
  • Mutation / genetics*
  • Parkinson Disease / genetics*
  • Sphingomyelin Phosphodiesterase / genetics*


  • Sphingomyelin Phosphodiesterase