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Effect of polygenic load on striatal dopaminergic deterioration in Parkinson disease

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dc.contributor.author류철형-
dc.date.accessioned2020-02-11T02:23:10Z-
dc.date.available2020-02-11T02:23:10Z-
dc.date.issued2019-
dc.identifier.issn0028-3878-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/174494-
dc.description.abstractOBJECTIVE: To investigate the effect of polygenic load on the progression of striatal dopaminergic dysfunction in patients with Parkinson disease (PD). METHODS: Using data from 335 patients with PD in the Parkinson's Progression Markers Initiative (PPMI) database, we investigated the longitudinal association of PD-associated polygenic load with changes in striatal dopaminergic activity as measured by 123I-N-3-fluoropropyl-2-β-carboxymethoxy-3β-(4-iodophenyl) nortropane (123I-FP-CIT) SPECT over 4 years. PD-associated polygenic load was estimated by calculating weighted genetic risk scores (GRS) using 1) all available 27 PD-risk single nucleotide polymorphisms (SNPs) in the PPMI database (GRS1) and 2) 23 SNPs with minor allele frequency >0.05 (GRS2). RESULTS: GRS1 and GRS2 were correlated with younger age at onset in patients with PD (GRS1, Spearman ρ = -0.128, p = 0.019; GRS2, Spearman ρ = -0.109, p = 0.047). Although GRS1 did not show an association with changes in striatal 123I-FP-CIT availability, GRS2 was associated with a slower decline of striatal dopaminergic activity (interactions with disease duration in linear mixed model; caudate nucleus, estimate = 0.399, SE = 0.165, p = 0.028; putamen, estimate = 0.396, SE = 0.137, p = 0.016). CONCLUSIONS: Our results suggest that genetic factors for PD risk may have heterogeneous effects on striatal dopaminergic degeneration, and some factors may be associated with a slower decline of dopaminergic activity. Composition of PD progression-specific GRS may be useful in predicting disease progression in patients.-
dc.description.statementOfResponsibilityrestriction-
dc.languageEnglish-
dc.publisherLippincott Williams & Wilkins-
dc.relation.isPartOfNEUROLOGY-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.subject.MESHAdult-
dc.subject.MESHAged-
dc.subject.MESHCaudate Nucleus/metabolism-
dc.subject.MESHCorpus Striatum/metabolism*-
dc.subject.MESHDisease Progression-
dc.subject.MESHDopamine Plasma Membrane Transport Proteins/metabolism-
dc.subject.MESHFemale-
dc.subject.MESHHumans-
dc.subject.MESHMale-
dc.subject.MESHMiddle Aged-
dc.subject.MESHParkinson Disease/complications-
dc.subject.MESHParkinson Disease/genetics-
dc.subject.MESHParkinson Disease/metabolism*-
dc.subject.MESHParkinsonian Disorders/complications-
dc.subject.MESHParkinsonian Disorders/metabolism*-
dc.subject.MESHPutamen/metabolism-
dc.subject.MESHTropanes/metabolism*-
dc.titleEffect of polygenic load on striatal dopaminergic deterioration in Parkinson disease-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Neurology (신경과학교실)-
dc.contributor.googleauthorMyung Jun Lee-
dc.contributor.googleauthorKyoungjune Pak-
dc.contributor.googleauthorJong Hun Kim-
dc.contributor.googleauthorYun Joong Kim-
dc.contributor.googleauthorJeehee Yoon-
dc.contributor.googleauthorJinwoo Lee-
dc.contributor.googleauthorChul Hyoung Lyoo-
dc.contributor.googleauthorHyung Jun Park-
dc.contributor.googleauthorJae-Hyeok Lee-
dc.contributor.googleauthorNa-Yeon Jung-
dc.identifier.doi10.1212/WNL.0000000000007939-
dc.contributor.localIdA01333-
dc.relation.journalcodeJ02340-
dc.identifier.eissn1526-632X-
dc.identifier.pmid31289143-
dc.identifier.urlhttps://n.neurology.org/content/93/7/e665.long-
dc.contributor.alternativeNameLyoo, Chul Hyoung-
dc.contributor.affiliatedAuthor류철형-
dc.citation.volume93-
dc.citation.number7-
dc.citation.startPagee665-
dc.citation.endPagee674-
dc.identifier.bibliographicCitationNEUROLOGY, Vol.93(7) : e665-e674, 2019-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers

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