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000282915 1001_ $$0P:(DE-HGF)0$$aSun, Wenhua$$b0$$eFirst author
000282915 245__ $$aTMEM175, SCARB2 and CTSB associations with Parkinson's disease risk across populations.
000282915 260__ $$a[London]$$bSpringer Nature$$c2025
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000282915 520__ $$aGenome-wide association study of Parkinson's disease (PD) identified common variants associated with lysosomal mechanism, including TMEM175, SCARB2, and CTSB. We investigated the association between common and rare variants across populations using cohorts from the Global Parkinson's Genetics Program (GP2) (33,733 cases and 18,703 controls from ten ancestries). In the European cohort, we confirmed significant associations with PD risk for all known genetic risk variants across the three genes and TMEM175 p. Met393Thr as an independent genome-wide significant signal. Additionally, a novel independent signal, SCARB2 rs11547135, was detected. The burden analysis linked PD to SCARB2 in African American, Ashkenazi Jewish and East Asian cohorts. Single variants-based tests identified rare missense variants in SCARB2 in several populations. Our study reinforces the association of lysosomal genetic variants with PD risk, revealing genetic heterogeneity across populations.
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