scholarly journals Analysis of PTRHD1 common and rare variants in European patients with Parkinson’s disease

2020 ◽  
Author(s):  
Yuri L. Sosero ◽  
Sara Bandres-Ciga ◽  
Ziv Gan-Or ◽  
Lynne Krohn
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Large Scale ◽  
Genome Wide Association Study ◽  
Rare Variants ◽  
Age At Onset ◽  
European Population ◽  
European Ancestry ◽  
Genome Wide ◽  
Meta Analyses

AbstractThree family studies identified three different variants in the peptidyl-tRNA hydrolase domain containing 1 gene (PTRHD1) in patients affected by syndromic parkinsonism. In the current study, our objective was to investigate whether PTRHD1 variants are associated with Parkinson’s disease (PD) risk and age at onset (AAO). To evaluate the association between PTRHD1 and PD risk, we analyzed whole genome sequencing (WGS) data of 1,647 PD cases and 1,050 healthy controls, as well as genome-wide imputed genotyping data on 14,671 PD cases and 17,667 controls, all of European ancestry. Furthermore, we examined the association of PTRHD1 with PD risk and AAO using summary statistics data from the most recent PD genome-wide association study (GWAS) meta-analyses. Our results show no association between PTRHD1 and PD risk or AAO. We conclude that PTRHD1 does not play a major role in PD in the European population. Further large-scale studies including subjects with different ancestry and family trios might further clarify the relationship of this gene with PD and atypical parkinsonism.

scholarly journals Analysis of 12 GWAS-Linked Loci With Parkinson’s Disease in the Chinese Han Population

2021 ◽  
Vol 12 ◽  
Author(s):  
Liyuan Fan ◽  
Changhe Shi ◽  
Xinchao Hu ◽  
Zhongxian Zhang ◽  
Huimin Zheng ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Large Scale ◽  
Genome Wide Association Study ◽  
Chinese Han Population ◽  
Chinese Han ◽  
Han Population ◽  
Asian Populations ◽  
Genome Wide ◽  
The Relationship

A recent large-scale European-originated genome-wide association study identified 38 novel independent risk signals in 37 loci for Parkinson's disease (PD). However, whether these new loci are associated with PD in Asian populations remains elusive. The present study aimed to explore the relationship between the 12 most relevant loci with larger absolute values for these new risk loci and PD in the Chinese Han population. We performed a case-control study including 527 PD patients and 435 healthy controls. In the allele model, it was found that rs10748818/GBF1 was associated with PD in the Chinese Han population [p = 0.035, odds ratio (OR) 1.221, 95% confidence interval (CI) 1.014–1.472

297 Genetic associations of ICD in parkinson’s disease

2018 ◽  
Vol 89 (10) ◽  
pp. A47.2-A47
Author(s):  
Rees Richard ◽  
Hubbard Leon ◽  
Ben-Shlomo Yoav ◽  
Grosset Donald ◽  
Williams Nigel ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Genome Wide Association Study ◽  
Early Stage ◽  
Age At Onset ◽  
Genetic Associations ◽  
Longitudinal Assessment ◽  
Genetic Determinants ◽  
Genome Wide ◽  
A Genome

IntroductionImpuse Control Disorders (ICD) are a potentially devastating side-effect of dopaminergic therapy in Parkinson’s disease (PD). We explore the genetic factors associated with ICD in Tracking Parkinson’s/PRoBaND – a UK-wide cohort of early-stage PD.MethodsParticipants were diagnosed with PD within 3 years and had longitudinal assessment including the Questionnaire for ICD in Parkinson’s (QUIP) for up to 5 years. We defined cases as having any positive response to the QUIP (lax criteria) or 2 positive responses in any domain (strict criteria). We performed a candidate-gene analysis based on systematic review, followed by a genome-wide association study. We used age at onset, gender, and three significant principle components as covariates.ResultsAfter clinical and genetic quality control steps, we analysed 1602 participants. Prevalence was significantly affected by classification criteria (strict/lax): ICD – 26.8%/11.1%, IRB 29.3%/27.2%, any 31.7%/41.9%. Six SNPs in dopamine, glutamate and adreno- receptor genes achieved nominal significance (p<0.05) in the candidate study. We have identified several SNPs in the GWAS that approach genome wide significance (p<5 × 10–7).ConclusionsThis work is the first genome-wide study of genetic determinants of ICD. Our findings support the hypothesis of genetic determinants of ICD in Parkinson’s and further work will allow understanding of the biology of ICD.

scholarly journals Common and rare variants in HFE are not associated with Parkinson’s disease in Europeans

2020 ◽  
Author(s):  
Prabhjyot Saini ◽  
Sara Bandres-Ciga ◽  
Jose Luis Alcantud ◽  
Clara Ruz ◽  
Ziv Gan-Or ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Iron Homeostasis ◽  
Genome Wide Association Study ◽  
Rare Variants ◽  
Common Variants ◽  
Sequencing Data ◽  
Differential Distribution ◽  
Logistic Regression Models ◽  
Genome Wide

AbstractA recent study suggested that the p.H63D variant in HFE, a gene involved in iron homeostasis, may modify α-synuclein pathology, the pathological hallmark of Parkinson’s disease (PD). If indeed this gene and specific variant are involved in PD, we expect to find differential distribution of HFE variants when comparing PD patients and controls. We analyzed genome-wide association study (GWAS) data from 14,671 PD patients and 17,667 controls and full sequencing data from additional 1,647 PD patients and 1,050 controls, using logistic regression models, and burden and Kernel tests. The HFE p.H63D variant was not associated with PD, nor did all the other common variants in the HFE locus. We did not find association of rare HFE variants with PD as well in all types of burden and Kernel tests. Our results do not support a role for HFE in PD.

scholarly journals Parkinson's disease age at onset genome‐wide association study: Defining heritability, genetic loci, and α‐synuclein mechanisms

2019 ◽  
Vol 34 (6) ◽  
pp. 866-875 ◽  
Author(s):  
Cornelis Blauwendraat ◽  
Karl Heilbron ◽  
Costanza L. Vallerga ◽  
Sara Bandres‐Ciga ◽  
Rainer von Coelln ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Age At Onset ◽  
Genome Wide Association ◽  
Genetic Loci ◽  
Genome Wide

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

2020 ◽  
Author(s):  
Dongbing Lai ◽  
Babak Alipanahi ◽  
Pierre Fontanillas ◽  
Tae-Hwi Schwantes-An ◽  
Jan Aasly ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Age At Onset ◽  
Genome Wide Association ◽  
P Value ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Genome Wide

Objective: The aim of this study was to search for genes/variants that modify the effect of LRRK2 mutations in terms of penetrance and age-at-onset of Parkinson's disease. Methods: We performed the first genome-wide association study of penetrance and age-at-onset of Parkinson's disease in LRRK2 mutation carriers (776 cases and 1,103 non-cases at their last evaluation). Cox proportional hazard models and linear mixed models were used to identify modifiers of penetrance and age-at-onset of LRRK2 mutations, respectively. We also investigated whether a polygenic risk score derived from a published genome-wide association study of Parkinson's disease was able to explain variability in penetrance and age-at-onset in LRRK2 mutation carriers. Results: A variant located in the intronic region of CORO1C on chromosome 12 (rs77395454; P-value=2.5E-08, beta=1.27, SE=0.23, risk allele: C) met genome-wide significance for the penetrance model. A region on chromosome 3, within a previously reported linkage peak for Parkinson's disease susceptibility, showed suggestive associations in both models (penetrance top variant: P-value=1.1E-07; age-at-onset top variant: P-value=9.3E-07). A polygenic risk score derived from publicly available Parkinson's disease summary statistics was a significant predictor of penetrance, but not of age-at-onset. Interpretation: This study suggests that variants within or near CORO1C may modify the penetrance of LRRK2 mutations. In addition, common Parkinson's disease associated variants collectively increase the penetrance of LRRK2 mutations.

scholarly journals Association between NMD3 and symptoms of Parkinson's disease in Chinese

2019 ◽  
Author(s):  
Hui Wu ◽  
Hui Li ◽  
Zhiqiang Shi ◽  
Jiajia Tang ◽  
Shuya Mei ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Large Scale ◽  
Rating Scale ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Southern Chinese ◽  
Genome Wide ◽  
Hamilton Anxiety Rating Scale ◽  
Meta Analyses

Abstract Bcakground: Parkinson's disease (PD) is a progresasive neurodegenerative movement disorder which is characterized by motor symptoms such as tremor, rigidity, slowness of movement and problems with gait. Large-scale meta-analyses of genome-wide association studies (GWAS) have identified few susceptibility loci in sporadic PD. The aim of this study was to investigate the association between NMD3 single nucleotide polymorphism (SNP) and symptoms of PD patients in southern Chinese. Methods: A total of 217 PD patients were recruited in this study and were genotyped by using SNaPshot technique and the polymer chain reaction. All subjects were evaluated by Mini-Mental State Examination (MMSE), Beijing version Montreal Cognitive Assessment (MoCA), Sniffin’ Sticks 16 (SS-16), Hamilton anxiety rating scale, Hamilton depression rating scale, 39-item Parkinson's disease Questionnaire (PDQ-39) and MDS Unified PD Rating Scale (MDS-UPDRS). Results: NMD3 rs34016896 (T) carriers have worse cognitive function (MMSE: p 0.042, NMD3wildtype: 27.44 ± 2.89, NMD3 carriers: 26.31 ± 3.79; MoCA: p 0.005, NMD3 wildtype: 23.15 ±4.20, NMD3 carriers: 20.75 ± 6.68). Conclusions: The recessive and overdominant model of NMD3 rs34016896 was associated with cognitive impairment in PD patients.

scholarly journals The Parkinson’s Disease GWAS Locus Browser

2020 ◽  
Author(s):  
Francis P. Grenn ◽  
Jonggeol J. Kim ◽  
Mary B. Makarious ◽  
Hirotaka Iwaki ◽  
Anastasia Illarionova ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Large Scale ◽  
Association Studies ◽  
Age At Onset ◽  
Genome Wide Association Studies ◽  
Functional Studies ◽  
Risk Variants ◽  
Genome Wide

AbstractParkinson’s disease (PD) is a neurodegenerative disease with an often complex genetic component identifiable by genome-wide association studies (GWAS). The most recent large scale PD GWASes have identified more than 90 independent risk variants for PD risk and progression across 80 loci. One major challenge in current genomics is identifying the causal gene(s) and variant(s) from each GWAS locus. Here we present a GWAS locus browser application that combines data from multiple databases to aid in the prioritization of genes associated with PD GWAS loci. We included 92 independent genome-wide significant signals from multiple recent PD GWAS studies including the PD risk GWAS, age-at-onset GWAS and progression GWAS. We gathered data for all 2336 genes within 1Mb up and downstream of each variant to allow users to assess which gene(s) are most associated with the variant of interest based on a set of self-ranked criteria. Our aim is that the information contained in this browser (https://pdgenetics.shinyapps.io/GWASBrowser/) will assist the PD research community with the prioritization of genes for follow-up functional studies and as potential therapeutic targets.

scholarly journals Assessment of LIN28A variants in Parkinson’s disease

2020 ◽  
Author(s):  
Monica Diez-Fairen ◽  
Mary B. Makarious ◽  
Sara Bandres-Ciga ◽  
Cornelis Blauwendraat
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Large Scale ◽  
Disease Risk ◽  
Age At Onset ◽  
European Ancestry ◽  
Whole Genome Sequencing Data ◽  
Sequencing Data ◽  
Common Genetic Variants

AbstractParkinson’s disease (PD) is a complex neurodegenerative disease with a strong genetic component in which both rare and common genetic variants contribute to disease risk, onset and progression. Despite that several genes have been associated with familial forms of disease, validation of novel genes associated with PD remains extremely challenging. Recently, a heterozygous loss-of-function variant in LIN28A was associated with PD pathogenesis in the Asian population. Here, we comprehensively assess the role of LIN28A variants in PD susceptibility using individual-level genotyping data from 14,671 PD cases and 17,667 controls, as well as whole-genome sequencing data from 1,647 PD patients and 1,050 controls. Additionally, we further assessed the summary statistics from the most recent GWAS meta-analyses to date for PD risk and age at onset. After evaluating these data, we did not find evidence to support a role for LIN28A as a major causal gene for PD. However, additional large-scale familial and case-control studies in non-European ancestry populations are necessary to further evaluate the role of LIN28A in PD etiology.

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