Smoking is associated with age at disease onset in Parkinson's disease

Parkinsonism Relat Disord. 2022 Apr:97:79-83. doi: 10.1016/j.parkreldis.2022.03.005. Epub 2022 Mar 24.


Background: Previous studies linked disease-progression variables such as age at onset or survival to both genetic, and non-genetic factors in Parkinson's disease (PD) patients.

Objective: The aim of this study was to assess how genetic and non genetic factors act as modifiers of age at onset and survival and in a cohort of 753 PD patients, and to determine how these variables interact to define the overall risk.

Methods: We analyzed the effect of gender, tobacco, alcohol, type of PD (genetic, gPD or idiopathic, iPD) and three genetic variants rs5848- GRN, rs1042522- TP53 and APOE. We studied two cohorts (PPMI and IPDGC) to replicate positive results.

Results: Regarding age at onset, male smokers PD had a significantly lower mean age compared to non-smoker (p = 0.001). APOE-Ɛ4 carriers had a younger onset-age compared to non-carriers (p = 0.03) in the Spanish cohort, but these results were not replicated in the other cohorts. Concerning survival, PD patients with an early onset (below 50 years) had an increased survival rate (p < 0.001).

Conclusions: Our study showed how several genetic and non-genetic risk factors influenced the age at onset and survival in PD.

Keywords: APOE; Age of onset; Parkinson disease; Smoking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Apolipoproteins E / genetics
  • Cohort Studies
  • Heterozygote
  • Humans
  • Male
  • Parkinson Disease* / complications
  • Parkinson Disease* / epidemiology
  • Parkinson Disease* / genetics
  • Smoking / adverse effects
  • Smoking / epidemiology


  • Apolipoproteins E