Genetic factors, environmental factors, and gene-environment interactions have been found to modify PD risk, age at onset (AAO), and disease progression. The objective of this study was to explore ...the association of coffee drinking, aspirin intake, and smoking, with motor and non-motor symptoms in a cohort of 35,959 American patients with PD from the Fox Insight Study using generalized linear models. Coffee drinkers had fewer problems swallowing but dosage and duration of coffee intake were not associated with motor or non-motor symptoms. Aspirin intake correlated with more tremor (p = 0.0026), problems getting up (p = 0.0185), light-headedness (p = 0.0043), and problems remembering (p = 1 × 10
). Smoking was directly associated with symptoms: smokers had more problems with drooling (p = 0.0106), swallowing (p = 0.0002), and freezing (p < 1 × 10
). Additionally, smokers had more possibly mood-related symptoms: unexplained pains (p < 1 × 10
), problems remembering (p = 0.0001), and feeling sad (p < 1 × 10
). Confirmatory and longitudinal studies are warranted to investigate the clinical correlation over time.
Abstract The objective of this study was to investigate the association between a Parkinson’s disease (PD)-specific polygenic score (PGS) and protective lifestyle factors on age at onset (AAO) in PD. ...We included data from 4367 patients with idiopathic PD, 159 patients with GBA1 -PD, and 3090 healthy controls of European ancestry from AMP-PD, PPMI, and Fox Insight cohorts. The association between PGS and lifestyle factors on AAO was assessed with linear and Cox proportional hazards models. The PGS showed a negative association with AAO ( β = − 1.07, p = 6 × 10 –7 ) in patients with idiopathic PD. The use of one, two, or three of the protective lifestyle factors showed a reduction in the hazard ratio by 21% ( p = 0.0001), 44% ( p < 2 × 10 –16 ), and 55% ( p < 2 × 10 –16 ), compared to no use. An additive effect of aspirin ( β = 7.62, p = 9 × 10 –7 ) and PGS ( β = − 1.58, p = 0.0149) was found for AAO without an interaction ( p = 0.9993) in the linear regressions, and similar effects were seen for tobacco. In contrast, no association between aspirin intake and AAO was found in GBA1 -PD ( p > 0.05). In our cohort, coffee, tobacco, aspirin, and PGS are independent predictors of PD AAO. Additionally, lifestyle factors seem to have a greater influence on AAO than common genetic risk variants with aspirin presenting the largest effect.
GBA1 variants are the strongest genetic risk factor for Parkinson's disease (PD). However, the pathogenicity of GBA1 variants concerning PD is still not fully understood. Additionally, the frequency ...of GBA1 variants varies widely across populations.
To evaluate Oxford Nanopore sequencing as a strategy, to determine the frequency of GBA1 variants in Norwegian PD patients and controls, and to review the current literature on newly identified variants that add to pathogenicity determination.
We included 462 Norwegian PD patients and 367 healthy controls. We sequenced the full-length GBA1 gene on the Oxford Nanopore GridION as an 8.9 kb amplicon. Six analysis pipelines were compared using two aligners (NGMLR, Minimap2) and three variant callers (BCFtools, Clair3, Pepper-Margin-Deepvariant). Confirmation of GBA1 variants was performed by Sanger sequencing and the pathogenicity of variants was evaluated.
We found 95.8% (115/120) true-positive GBA1 variant calls, while 4.2% (5/120) variant calls were false-positive, with the NGMLR/Minimap2-BCFtools pipeline performing best. In total, 13 rare GBA1 variants were detected: two were predicted to be (likely) pathogenic and eleven were of uncertain significance. The odds of carrying one of the two common GBA1 variants, p.L483P or p.N409S, in PD patients were estimated to be 4.11 times the odds of carrying one of these variants in controls (OR = 4.11 1.39, 12.12).
In conclusion, we have demonstrated that Oxford long-read Nanopore sequencing, along with the NGMLR/Minimap2-BCFtools pipeline is an effective tool to investigate GBA1 variants. Further studies on the pathogenicity of GBA1 variants are needed to assess their effect on PD.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
4.
How Do I Report Genes in a Paper? Gabbert, Carolin; Klein, Christine; Trinh, Joanne
Movement disorders clinical practice (Hoboken, N.J.),
20/May , Letnik:
11, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Genetic testing, including whole genome, whole exome, and other next‐generation sequencing technologies, has evolved vastly in the past decade. With this, the number of identified genes and genetic ...variants is constantly increasing. Although a variety of databases and online tools exist that summarize, categorize, and classify genes, a clear guideline of which information is needed when reporting a gene and what to do when identifying a new gene is lacking. This includes the correct nomenclature, descriptive information about genetic loci and genetic variation, aliases, and correlated phenotypes. This tutorial is meant to serve as an introduction to reporting genes in a paper and provides an overview of available databases and tools to obtain all necessary information on the genes of interest.
Parkinson’s disease (PD) is a progressive neurodegenerative disorder. Genetic modifiers, environmental factors and gene–environment interactions have been found to modify PD risk and disease ...progression. The objective of this study was to evaluate the association of smoking, caffeine and anti-inflammatory drugs with age at onset (AAO) in a large PD cohort. A total of 35,963 American patients with idiopathic PD (iPD) from the Fox Insight Study responded to health and lifestyle questionnaires. We compared the median AAO between different groups using the non-parametric Mann–Whitney
U
test. Non-parametric Spearman’s correlation was used for correlation assessments and regression analysis was used to assess interaction between variables. We found that smoking (
p
< 0.0001), coffee drinking (
p
< 0.0001) and aspirin intake (
p
< 0.0001) show an exploratory association with AAO in PD, that was further supported by multivariate regression models. The association of aspirin with PD AAO was replicated in another cohort (EPIPARK) (
n
= 237 patients with PD).
There have been no specific guidelines regarding which genes should be tested in the clinical setting for Parkinson's disease (PD) or parkinsonism. We evaluated the types of clinical genetic testing ...offered for PD as the first step of our gene curation.
The National Institutes of Health (NIH) Genetic Testing Registry (GTR) was queried on 12/7/2020 to identify current commercial PD genetic test offerings by clinical laboratories, internationally.
We identified 502 unique clinical genetic tests for PD, from 28 Clinical Laboratory Improvement Amendments (CLIA)-approved clinical laboratories. These included 11 diagnostic PD panels. The panels were notable for their differences in size, ranging from 5 to 62 genes. Five genes for variant query were included in all panels (SNCA, PRKN, PINK-1, PARK7 (DJ1), and LRRK2). Notably, the addition of the VPS35 and GBA genes was variable. Panel size differences stemmed from inclusion of genes linked to atypical parkinsonism and dystonia disorders, and genes in which the link to PD causation is controversial.
There is an urgent need for expert opinion regarding which genes should be included in a commercial laboratory multi-gene panel for PD.
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