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Peer-reviewedCC BY 4.0Frontiers in Neurology

Risk factors for early-onset Parkinson’s disease

  • Lu-Yao Li1,2
  • Zhe-Ming Yue3
  • Bo-Wen Zhang2,4
  • Fei-Yang Wang2
  • Shou-Ping Gong1,5
  • Yong-Xin Li2
5 affiliations
  1. 1Department of Neurosurgery, The Second Affiliated Hospital of Xi'an Jiaotong University
  2. 2Department of Cardiovascular Surgery, The First Affiliated Hospital of Xi'an Jiaotong University
  3. 3Department of Neurosurgery, 3201 Hospital
  4. 4School of Public Health, Xi'an Jiaotong University
  5. 5Xi’an Medical University
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Abstract

Background: Prospective evidence on factors associated with early-onset Parkinson’s disease (EOPD) remains limited. We aimed to identify factors associated with incident EOPD and compare their associations with late-onset Parkinson’s disease (LOPD).

Methods: This prospective cohort study included 283,934 participants aged <60 years and free of Parkinson’s disease at baseline. Thirty-eight prespecified factors were evaluated using Cox regression with Benjamini–Hochberg false discovery rate correction, followed by an exploratory mutually adjusted analysis. Sex-stratified and EOPD–LOPD comparative analyses were conducted, and sensitivity analyses excluded EOPD events occurring within the first 2 or 5 years of follow-up.

Results: During 2,298,992 person-years of follow-up, 168 participants developed EOPD. After mutual adjustment, EOPD was associated with older age [hazard ratio (HR) per year, 1.15; 95% confidence interval (CI), 1.10–1.20], male sex (HR, 1.93; 95% CI, 1.41–2.64), a higher polygenic risk score (HR per unit, 1.53; 95% CI, 1.31–1.78), family history of Parkinson’s disease (HR, 4.03; 95% CI, 2.49–6.50), anxiety (HR, 2.48; 95% CI, 1.60–3.86), constipation (HR, 4.90; 95% CI, 3.31–7.25), and autoimmune disease burden (HR per category, 1.98; 95% CI, 1.32–2.96). Associations with handgrip strength, hypertension, and migraine were attenuated after mutual adjustment. The principal associations were broadly consistent after excluding EOPD events occurring within the first 2 and 5 years of follow-up. Interaction tests suggested stronger associations of family history, constipation, and autoimmune disease burden with EOPD than with LOPD.

Conclusion: EOPD showed a distinct profile of associated risk factors, particularly greater autoimmune disease burden and familial susceptibility. These findings support heterogeneity in Parkinson’s disease according to age at onset.

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Cite

BibTeXRIS
BibTeX
@article{li2026risk,
  title = {{Risk factors for early-onset Parkinson’s disease}},
  author = {Lu-Yao Li and Zhe-Ming Yue and Bo-Wen Zhang and Fei-Yang Wang and Shou-Ping Gong and Yong-Xin Li},
  journal = {Frontiers in Neurology},
  year = {2026},
  month = nov,
  doi = {10.3389/fneur.2026.1938082},
  url = {https://www.frontiersin.org/articles/10.3389/fneur.2026.1938082/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Risk factors for early-onset Parkinson’s disease
AU  - Lu-Yao Li
AU  - Zhe-Ming Yue
AU  - Bo-Wen Zhang
AU  - Fei-Yang Wang
AU  - Shou-Ping Gong
AU  - Yong-Xin Li
PY  - 2026
DA  - 2026/11/02
JO  - Frontiers in Neurology
DO  - 10.3389/fneur.2026.1938082
UR  - https://www.frontiersin.org/articles/10.3389/fneur.2026.1938082/full
AB  - Background: Prospective evidence on factors associated with early-onset Parkinson’s disease (EOPD) remains limited. We aimed to identify factors associated with incident EOPD and compare their associations with late-onset Parkinson’s disease (LOPD).  Methods: This prospective cohort study included 283,934 participants aged <60 years and free of Parkinson’s disease at baseline. Thirty-eight prespecified factors were evaluated using Cox regression with Benjamini–Hochberg false discovery rate correction, followed by an exploratory mutually adjusted analysis. Sex-stratified and EOPD–LOPD comparative analyses were conducted, and sensitivity analyses excluded EOPD events occurring within the first 2 or 5 years of follow-up.  Results: During 2,298,992 person-years of follow-up, 168 participants developed EOPD. After mutual adjustment, EOPD was associated with older age [hazard ratio (HR) per year, 1.15; 95% confidence interval (CI), 1.10–1.20], male sex (HR, 1.93; 95% CI, 1.41–2.64), a higher polygenic risk score (HR per unit, 1.53; 95% CI, 1.31–1.78), family history of Parkinson’s disease (HR, 4.03; 95% CI, 2.49–6.50), anxiety (HR, 2.48; 95% CI, 1.60–3.86), constipation (HR, 4.90; 95% CI, 3.31–7.25), and autoimmune disease burden (HR per category, 1.98; 95% CI, 1.32–2.96). Associations with handgrip strength, hypertension, and migraine were attenuated after mutual adjustment. The principal associations were broadly consistent after excluding EOPD events occurring within the first 2 and 5 years of follow-up. Interaction tests suggested stronger associations of family history, constipation, and autoimmune disease burden with EOPD than with LOPD.  Conclusion: EOPD showed a distinct profile of associated risk factors, particularly greater autoimmune disease burden and familial susceptibility. These findings support heterogeneity in Parkinson’s disease according to age at onset.
SN  - 1664-2295
ER  -