Validity and Prognostic Value of a Polygenic Risk Score for Parkinson’s Disease

Koch, Sebastian; Laabs, Björn‐Hergen; Kasten, Meike; Vollstedt, Eva‐Juliane; Becktepe, Jos S.; Brüggemann, Norbert; Franke, André; Krämer, Ulrike M.; Kuhlenbäumer, Gregor; Lieb, Wolfgang; Mollenhauer, Brit; Neis, Miriam; Trenkwalder, Claudia; Schäffer, Eva; Usnich, Tatiana; Wittig, Michael; Klein, Christine; König, Inke R.; Lohmann, Katja; Krawczak, Michael; Caliebe, Amke

doi:10.3390/genes12121859

Cited by 19 publications

(21 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…between 0.8 – 1.2) 11 . Indeed, the current predictive ability of the SNPs associated with PD is so low as to make meaningful risk score prognosis unfeasible 29 . The missing heritability can partly be explained by issues with merging the multiple different diseases that contribute to PD, into the single entity that is defined by late-stage pathological markers (i.e., performing GWAS from the perspective of PD being a single disease).…”

Section: Using ‘Omics To Inform Origins and Trajectories Of Parkinson...mentioning

confidence: 99%

Redefining the hypotheses driving Parkinson’s diseases research

Farrow

Cooper

O’Sullivan

2022

npj Parkinsons Dis.

View full text Add to dashboard Cite

Parkinson’s disease (PD) research has largely focused on the disease as a single entity centred on the development of neuronal pathology within the central nervous system. However, there is growing recognition that PD is not a single entity but instead reflects multiple diseases, in which different combinations of environmental, genetic and potential comorbid factors interact to direct individual disease trajectories. Moreover, an increasing body of recent research implicates peripheral tissues and non-neuronal cell types in the development of PD. These observations are consistent with the hypothesis that the initial causative changes for PD development need not occur in the central nervous system. Here, we discuss how the use of neuronal pathology as a shared, qualitative phenotype minimises insights into the possibility of multiple origins and aetiologies of PD. Furthermore, we discuss how considering PD as a single entity potentially impairs our understanding of the causative molecular mechanisms, approaches for patient stratification, identification of biomarkers, and the development of therapeutic approaches to PD. The clear consequence of there being distinct diseases that collectively form PD, is that there is no single biomarker or treatment for PD development or progression. We propose that diagnosis should shift away from the clinical definitions, towards biologically defined diseases that collectively form PD, to enable informative patient stratification. N-of-one type, clinical designs offer an unbiased, and agnostic approach to re-defining PD in terms of a group of many individual diseases.

show abstract

Section: Using ‘Omics To Inform Origins and Trajectories Of Parkinson...mentioning

confidence: 99%

Redefining the hypotheses driving Parkinson’s diseases research

Farrow

Cooper

O’Sullivan

2022

npj Parkinsons Dis.

View full text Add to dashboard Cite

show abstract

“…Additionally, the disease is associated with non-motor symptoms that contribute to overall disability. Parkinson’s disease is distinguished by neuronal loss in the substantia nigra, striatal dopamine deficiency, and intracellular inclusions containing alpha-synuclein aggregates [ 119 , 120 , 121 , 122 ]. Recent studies suggest that the development of PD involves multiple factors, including impaired mitochondrial function, oxidative and nitrative stress, the buildup of misfolded proteins, and dysfunction of the ubiquitin-proteasome system.…”

Section: The Significance Of Adopting An Anti-inflammatory Diet For T...mentioning

confidence: 99%

“…Mediterranean diet, which is high in plant-based foods, fish, and olive oil, has been linked to a reduced risk of Parkinson’s disease [ 124 ]. Conversely, a diet high in saturated fat and cholesterol has been linked to an increased risk of PD [ 122 ]. Therefore, patients with PD may benefit from dietary counseling to optimize their nutrition and reduce their risk of disease progression.…”

Section: The Significance Of Adopting An Anti-inflammatory Diet For T...mentioning

confidence: 99%

The Role of Diet as a Modulator of the Inflammatory Process in the Neurological Diseases

et al. 2023

View full text Add to dashboard Cite

Neurological diseases are recognized as major causes of disability and mortality worldwide. Due to the dynamic progress of diseases such as Alzheimer’s disease (AD), Parkinson’s Disease (PD), Schizophrenia, Depression, and Multiple Sclerosis (MD), scientists are mobilized to look for new and more effective methods of interventions. A growing body of evidence suggests that inflammatory processes and an imbalance in the composition and function of the gut microbiome, which play a critical role in the pathogenesis of various neurological diseases and dietary interventions, such as the Mediterranean diet the DASH diet, or the ketogenic diet can have beneficial effects on their course. The aim of this review was to take a closer look at the role of diet and its ingredients in modulating inflammation associated with the development and/or progression of central nervous system diseases. Presented data shows that consuming a diet abundant in fruits, vegetables, nuts, herbs, spices, and legumes that are sources of anti-inflammatory elements such as omega-3 fatty acids, polyphenols, vitamins, essential minerals, and probiotics while avoiding foods that promote inflammation, create a positive brain environment and is associated with a reduced risk of neurological diseases. Personalized nutritional interventions may constitute a non-invasive and effective strategy in combating neurological disorders.

show abstract

“…One way to assess the cumulative effect of genetic variants on disease risk or AAO is by deriving and using a polygenic score (PGS). 7,8 Previously, a mitochondrial polygenic score (MGS) was derived and composed of genes involved in mitophagy, mitochondrial bioenergetics and proteostasis pathways. The study nominated 14 SNPs as causally associated with mitochondrial function and PD risk by Mendelian randomization.…”

Section: Introductionmentioning

confidence: 99%

Interaction of mitochondrial polygenic score and environmental factors in LRRK2 p.Gly2019Ser parkinsonism

Lueth

Gabbert

Koenig

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

The objective of our study was to investigate the impact of the mitochondrial polygenic score (MGS) and lifestyle/environmental data on age at onset in LRRK2 p.Gly2019Ser parkinsonism (LRRK2-PD) and idiopathic Parkinson's disease (iPD). In this study, we included N=486 patients with LRRK2-PD and N=9259 patients with iPD from AMP-PD, Fox Insight, and a Tunisian Arab-Berber founder population. Genotyping data was utilized to perform the MGS analysis, using 14 Single Nucleotide Polymorphisms (SNPs) from genes causally associated with mitochondrial function and PD risk. Additionally, lifestyle and environmental data were obtained from the PD risk factor questionnaire (PD-RFQ). Correlation analyses and linear regression models were used to assess the relationship between MGS, lifestyle/environment, and AAO. We observed that higher MGS was associated with earlier AAO in patients with LRRK2-PD (p=4.0x10-4, beta=-0.18) but not in patients with iPD. A correlation between MGS and AAO was visibly stronger in European ancestry LRRK2-PD patients (p=0.01, r=-0.16) than in Tunisian Arab-Berber patients (p=0.44, r=-0.05). We found that the MGS interacted with coffee (p=0.03, beta=-0.38) and caffeinated soda consumption (p=0.03, beta=-0.37) in LRRK2-PD and with caffeine soda consumption (p=0.047, beta=-0.22) and pesticide exposure (p=0.02, beta=-0.37) in iPD. Thus, patients with a high MGS had an earlier AAO only if they consumed caffeine or were exposed to pesticides. The MGS related to mitochondrial function was associated with AAO in LRRK2-PD but not iPD with an ethnic-specific effect. Caffeine consumption or pesticide exposure interacted with MGS to predict PD AAO. Our study suggests gene-environment interactions as modifiers of AAO in LRRK2-PD.

show abstract

Validity and Prognostic Value of a Polygenic Risk Score for Parkinson’s Disease

Cited by 19 publications

References 41 publications

Redefining the hypotheses driving Parkinson’s diseases research

Redefining the hypotheses driving Parkinson’s diseases research

The Role of Diet as a Modulator of the Inflammatory Process in the Neurological Diseases

Interaction of mitochondrial polygenic score and environmental factors in LRRK2 p.Gly2019Ser parkinsonism

Contact Info

Product

Resources

About