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dc.contributor.authorAlfradique-Dunham, Isabel
dc.contributor.authorAl-Ouran, Rami
dc.contributor.authorvon Coelln, Rainer
dc.contributor.authorBlauwendraat, Cornelis
dc.contributor.authorHill, Emily
dc.contributor.authorLuo, Lan
dc.contributor.authorStillwell, Amanda
dc.contributor.authorYoung, Emily
dc.contributor.authorKaw, Anita
dc.contributor.authorTan, Manuela
dc.contributor.authorLiao, Calwing
dc.contributor.authorHernandez, Dena
dc.contributor.authorPihlstrom, Lasse
dc.contributor.authorGrosset, Donald
dc.contributor.authorShulman, Lisa M
dc.contributor.authorLiu, Zhandong
dc.contributor.authorRouleau, Guy A
dc.contributor.authorNalls, Mike
dc.contributor.authorSingleton, Andrew B
dc.contributor.authorMorris, Huw
dc.contributor.authorJankovic, Joseph
dc.contributor.authorShulman, Joshua M
dc.date.accessioned2021-05-17T13:14:45Z
dc.date.available2021-05-17T13:14:45Z
dc.date.issued2021-01-28
dc.identifier.urihttp://hdl.handle.net/10713/15653
dc.description.abstractObjective: To discover genetic determinants of Parkinson disease (PD) motor subtypes, including tremor dominant (TD) and postural instability/gait difficulty (PIGD) forms. Methods: In 3,212 PD cases of European ancestry, we performed a genome-wide association study (GWAS) examining 2 complementary outcome traits derived from the Unified Parkinson's Disease Rating Scale, including dichotomous motor subtype (TD vs PIGD) or a continuous tremor/PIGD score ratio. Logistic or linear regression models were adjusted for sex, age at onset, disease duration, and 5 ancestry principal components, followed by meta-analysis. Results: Among 71 established PD risk variants, we detected multiple suggestive associations with PD motor subtype, including GPNMB (rs199351, psubtype = 0.01, pratio = 0.03), SH3GL2 (rs10756907, psubtype = 0.02, pratio = 0.01), HIP1R (rs10847864, psubtype = 0.02), RIT2 (rs12456492, psubtype = 0.02), and FBRSL1 (rs11610045, psubtype = 0.02). A PD genetic risk score integrating all 71 PD risk variants was also associated with subtype ratio (p = 0.026, ß = −0.04, 95% confidence interval = −0.07–0). Based on top results of our GWAS, we identify a novel suggestive association at the STK32B locus (rs2301857, pratio = 6.6 × 10−7), which harbors an independent risk allele for essential tremor. Conclusions: Multiple PD risk alleles may also modify clinical manifestations to influence PD motor subtype. The discovery of a novel variant at STK32B suggests a possible overlap between genetic risk for essential tremor and tremor-dominant PD.en_US
dc.description.urihttps://doi.org/10.1212/NXG.0000000000000557en_US
dc.description.urihttp://www.ncbi.nlm.nih.gov/pmc/articles/pmc8112852/en_US
dc.language.isoenen_US
dc.publisherWolters Kluwer Healthen_US
dc.relation.ispartofNeurology. Geneticsen_US
dc.rightsCopyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.en_US
dc.subject.meshGenome-Wide Association Studyen_US
dc.subject.meshParkinson Disease--geneticsen_US
dc.titleGenome-Wide Association Study Meta-Analysis for Parkinson Disease Motor Subtypesen_US
dc.typeArticleen_US
dc.identifier.doi10.1212/NXG.0000000000000557
dc.identifier.pmid33987465
dc.source.volume7
dc.source.issue2
dc.source.beginpagee557
dc.source.endpage
dc.source.countryUnited States


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