ArticleResearch square2026
Genome-wide association studies identify genetic determinants of synucleinopathy biomarkers.
Article in Research square, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: α-Synucleinopathies are clinically and biologically heterogeneous disorders lacking reliable biomarkers to assist with early diagnosis, disease progression, patient stratification, and therapeutic targeting. Genetic variation is known to impact biomarker levels, influencing their utility and interpretation in research and clinical settings. We aimed to identify common genetic modulators of biomarker levels implicated in α-synucleinopathy pathogenesis. Methods: 63 CSF, plasma, and urine biomarkers were analyzed in 581 individuals from the Parkinson's Progression Markers Initiative (PPMI). GWAS was performed to test for associations with common variants, while regressions and area under the curve (AUC) analysis was used to assess predictive power. Analyses were adjusted for age, sex, disease status, and principal components. PD- and DLB-risk loci associations were separately assessed for each GWAS. Results: We confirm strong associations between urine bis(monoacylglycerol)phosphate (BMP) isoforms and the variants Conclusions: The present study reveals established and novel genetic modulators of potential α-synucleinopathy biomarkers, demonstrating that genetic background significantly shapes biomarker levels. These genetic influences should be accounted for when conducting biomarker-based research, clinical trials, or therapeutic development to ensure accurate interpretation and improve their translational relevance.
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