scholarly journals A meta-analysis of genome-wide association studies identifies 17 new Parkinson's disease risk loci

2017 ◽  
Vol 49 (10) ◽  
pp. 1511-1516 ◽  
Author(s):  
Diana Chang ◽  
◽  
Mike A Nalls ◽  
Ingileif B Hallgrímsdóttir ◽  
Julie Hunkapiller ◽  
...  
2019 ◽  
Vol 18 (12) ◽  
pp. 1091-1102 ◽  
Author(s):  
Mike A Nalls ◽  
Cornelis Blauwendraat ◽  
Costanza L Vallerga ◽  
Karl Heilbron ◽  
Sara Bandres-Ciga ◽  
...  

2020 ◽  
Author(s):  
Manuela MX Tan ◽  
Michael A Lawton ◽  
Edwin Jabbari ◽  
Regina H Reynolds ◽  
Hirotaka Iwaki ◽  
...  

Background: There are currently no treatments that stop or slow the progression of Parkinson's disease (PD). Case-control genome-wide association studies (GWASs) have identified variants associated with disease risk, but not progression. Objective: To identify genetic variants associated with PD progression in GWASs. Methods: We analysed three large, longitudinal cohorts: Tracking Parkinson's, Oxford Discovery, and the Parkinson's Progression Markers Initiative. We included clinical data for 3,364 patients with 12,144 observations (mean follow-up 4.2 years). We used a new method in PD, following a similar approach in Huntington's disease, where we combined multiple assessments using a principal components analysis to derive scores for composite, motor, and cognitive progression. These scores were analysed in linear regressions in GWASs. We also performed a targeted analysis of the 90 PD risk loci from the latest case-control meta-analysis. Results: There was no overlap between variants associated with PD risk, from case-control studies, and PD age at onset versus PD progression. The APOE ϵ4 tagging variant, rs429358, was significantly associated with the rate of composite and cognitive progression in PD. No single variants were associated with motor progression. However in gene-based analysis, variation across ATP8B2, a phospholipid transporter related to vesicle formation, was nominally associated with motor progression (p=5.3 x 10^-6). Conclusions: This new method in PD improves measurement of symptom progression. We provide strong evidence that the APOE ϵ4 allele drives progressive cognitive impairment in PD. We have also reported loci of interest which need to be tested in further studies.


2021 ◽  
Author(s):  
Dongbing Lai ◽  
Babak Alipanahi ◽  
Pierre Fontanillas ◽  
Tae‐Hwi Schwantes‐An ◽  
Jan Aasly ◽  
...  

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Kuo-Hsuan Chang ◽  
Chiung-Mei Chen ◽  
Yi-Chun Chen ◽  
Hon-Chung Fung ◽  
Yih-Ru Wu

Previous genome-wide association studies in Caucasian populations suggest that genetic loci in amino acid catabolism may be associated with Parkinson’s disease (PD). However, these genetic disease associations were limitedly reported in Asian populations. Herein, we investigated the effect of top three PD-associated genetic variants related to amino acid catabolism in Caucasians listed on the top risk loci identified by meta-analysis of genome-wide association studies in PDGene database, including aminocarboxymuconate-semialdehyde decarboxylase- (ACMSD-) transmembrane protein 163 (TMEM163) rs6430538, methylcrotonyl-CoA carboxylase 1 (MCCC1) rs12637471, and branched-chain ketoacid dehydrogenase kinase- (BCKDK-) syntaxin 1B (STX1B) rs14235, by genotyping 599 Taiwanese patients with PD and 598 age-matched control subjects. PD patients demonstrate similar allelic and genotypic frequencies in all tested genetic variants. These ethnic discrepancies of genetic variants suggest a distinct genetic background of amino acid catabolism between Taiwanese and Caucasian PD patients.


2013 ◽  
Vol 34 (6) ◽  
pp. 1708.e7-1708.e13 ◽  
Author(s):  
Lasse Pihlstrøm ◽  
Gunnar Axelsson ◽  
Kari Anne Bjørnarå ◽  
Nil Dizdar ◽  
Camilla Fardell ◽  
...  

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