Assessing Genetic Overlap Between Platelet Parameters and Neurodegenerative Disorders

Area of Science:

• Genetics
• Neuroscience
• Hematology

Background:

• Neurodegenerative diseases like Parkinson's disease (PD) and Alzheimer's disease (AD) lack early predictive biomarkers, delaying diagnosis until symptoms manifest.
• Platelet parameters are potential biomarkers for PD and AD, but their genetic underpinnings remain underexplored.

Purpose of the Study:

• To investigate the genome-wide genetic correlation between platelet parameters and the risk of PD and AD.
• To explore the shared genetic basis between platelet distribution width (PDW) and neurodegenerative disease risk.

Main Methods:

• Linkage Disequilibrium Score Regression (LDSC) was employed to assess genome-wide coheritability between platelet parameters and PD/AD risk.
• Summary-summary polygenic score analysis was used to confirm findings and quantify the proportion of risk explained by PDW.

Main Results:

• A significant positive genetic correlation was found between platelet distribution width (PDW) and PD risk (rg = 0.080, p = 0.019).
• PDW explained a small but significant proportion (<1%) of PD risk, confirmed by polygenic score analysis.
• No significant genetic correlation was observed between PDW and AD risk, though a trend suggested a negative association (rg = -0.088, p = 0.096).

Conclusions:

• Limited shared genetic factors exist between PDW and PD risk, necessitating further research to identify specific genes.
• The association between platelet parameters and AD risk is likely influenced more by environmental factors than shared genetics.