scholarly journals No genetic evidence for involvement of alcohol dehydrogenase genes in risk for Parkinson’s disease

2019 ◽  
Author(s):  
Jonggeol Jeffrey Kim ◽  
Sara Bandres-Ciga ◽  
Cornelis Blauwendraat ◽  
Ziv Gan-Or ◽  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Genetic Variation ◽  
Alcohol Dehydrogenase ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Causal Gene ◽  
Risk Variants ◽  
Genome Wide

AbstractMultiple genes have been implicated in Parkinson’s disease (PD), including causal gene variants and risk variants typically identified using genome-wide association studies (GWAS). Variants in the alcohol dehydrogenase genes ADH1C and ADH1B are among the genes that have been associated with PD, suggesting that this family of genes may be important in PD. As part of the International Parkinson’s Disease Genomics Consortium’s (IPDGC) efforts to scrutinize previously reported risk factors for PD, we explored genetic variation in the alcohol dehydrogenase genes ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH6, and ADH7 using imputed GWAS data from 15,097 cases and 17,337 healthy controls. Rare-variant association tests and single-variant score tests did not show any statistically significant association of alcohol dehydrogenase genetic variation with the risk for PD.

scholarly journals Genome‐wide association studies of LRRK2 modifiers of Parkinson's disease

2021 ◽  
Author(s):  
Dongbing Lai ◽  
Babak Alipanahi ◽  
Pierre Fontanillas ◽  
Tae‐Hwi Schwantes‐An ◽  
Jan Aasly ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide

scholarly journals Polymorphisms of ACMSD-TMEM163, MCCC1, and BCKDK-STX1B Are Not Associated with Parkinson’s Disease in Taiwan

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Kuo-Hsuan Chang ◽  
Chiung-Mei Chen ◽  
Yi-Chun Chen ◽  
Hon-Chung Fung ◽  
Yih-Ru Wu
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Amino Acid ◽  
Genetic Variants ◽  
Transmembrane Protein ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Amino Acid Catabolism ◽  
Genome Wide

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.

scholarly journals Supportive evidence for 11 loci from genome-wide association studies in Parkinson's disease

2013 ◽  
Vol 34 (6) ◽  
pp. 1708.e7-1708.e13 ◽  
Author(s):  
Lasse Pihlstrøm ◽  
Gunnar Axelsson ◽  
Kari Anne Bjørnarå ◽  
Nil Dizdar ◽  
Camilla Fardell ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Supportive Evidence ◽  
Genome Wide

scholarly journals Identification of novel risk loci, causal insights, and heritable risk for Parkinson's disease: a meta-analysis of genome-wide association studies

2019 ◽  
Vol 18 (12) ◽  
pp. 1091-1102 ◽  
Author(s):  
Mike A Nalls ◽  
Cornelis Blauwendraat ◽  
Costanza L Vallerga ◽  
Karl Heilbron ◽  
Sara Bandres-Ciga ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Association Studies ◽  
Meta Analysis ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide

scholarly journals Genome-wide association studies of cognitive and motor progression in Parkinson's disease

2020 ◽  
Author(s):  
Manuela MX Tan ◽  
Michael A Lawton ◽  
Edwin Jabbari ◽  
Regina H Reynolds ◽  
Hirotaka Iwaki ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Risk ◽  
Association Studies ◽  
Age At Onset ◽  
Case Control ◽  
New Method ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide

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.

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