| Title: | Lower Lymphocyte Count is Associated With Increased Risk of Parkinson's Disease |
| Journal: | Annals of Neurology |
| Published: | 22 Feb 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/33527442/ |
| DOI: | https://doi.org/10.1002/ana.26034 |
| URL: | https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ana.26034 |
Publication 5346
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
OBJECTIVES: Patients with established Parkinson's disease (PD) display differences in peripheral blood markers of immune function, including leukocyte differential counts, compared with controls. These differences may be useful biomarkers to predict PD and may shed light on pathogenesis. We sought to identify whether peripheral immune dysregulation was associated with increased risk of subsequent PD diagnosis.</p>
METHODS: We examined the relationship between incident PD, baseline differential leukocyte count and other blood markers of acute inflammation in UK Biobank (UKB), a longitudinal cohort with ~500,000 participants. We used a range of sensitivity analyses and Mendelian randomization (MR) to further explore the nature of associations.</p>
RESULTS: After excluding individuals with comorbidities which could influence biomarkers of inflammation, 465 incident PD cases and 312,125 controls remained. Lower lymphocyte count was associated with increased risk of subsequent PD diagnosis (per 1-SD decrease in lymphocyte count odds ratio [OR] = 1.18, 95% confidence interval [CI] = 1.07-1.32, padjusted = 0.01). There was some evidence that reductions in eosinophil counts, monocyte counts and C-reactive protein (CRP) were associated with increased PD risk, and that higher neutrophil count was also associated. Only the association between lower lymphocyte count and increased PD risk remained robust to sensitivity analyses. MR suggested that the effect of lower lymphocyte count on PD risk may be causal (per 1-SD decrease in lymphocyte count; ORMR = 1.09, 95% CI = 1.01-1.18, p = 0.02).</p>
INTERPRETATION: We provide converging evidence from observational analyses in UKB and MR that lower lymphocyte count is associated with an increased risk of subsequent PD. ANN NEUROL 2021;89:803-812.</p>
19 Keywords
- Adult
- Aged
- Biological Specimen Banks
- Biomarkers
- C-Reactive Protein
- Cohort Studies
- Eosinophils
- Female
- Humans
- Immunity, Cellular
- Inflammation
- Longitudinal Studies
- Lymphocyte Count
- Male
- Mendelian Randomization Analysis
- Middle Aged
- Neutrophils
- Parkinson Disease
- Risk Assessment
8 Authors
- Melanie P. Jensen
- Benjamin Meir Jacobs
- Ruth Dobson
- Sara Bandres-Ciga
- Cornelis Blauwendraat
- Anette Schrag
- Alastair J. Noyce
- The International Parkinson's Disease Genomics Consortium
Enabling scientific discoveries that improve human health