Polygenic Risk Scores Contribute to Personalized Medicine of Parkinson’s Disease

Dehestani, Mohammad; Liu, Hui; Gasser, Thomas

doi:10.3390/jpm11101030

Cited by 16 publications

(21 citation statements)

References 69 publications

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“…This has recently been pointed out by several studies conducted in the Caucasian population from which a cohort of Slovenian patients included in the reported study originate as well. The latter confirms the reliability of this finding, which should be accounted for in future polygenic risk scores for prediction of PD since none of them so far take into account the VDR genotype ( Ibanez et al, 2017 ; Dehestani et al, 2021 ). Additionally, patients with at risk VDR genotypes are suitable candidates for close monitoring of vitamin D levels.…”

Section: Discussionsupporting

confidence: 78%

Genetic Variability of the Vitamin D Receptor Affects Susceptibility to Parkinson’s Disease and Dopaminergic Treatment Adverse Events

Redenšek

Kristanc

Blagus

et al. 2022

Front. Aging Neurosci.

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Vitamin D is a lipid-soluble molecule and an important transcriptional regulator in many tissues and organs, including the brain. Its role has been demonstrated also in Parkinson’s disease (PD) pathogenesis. Vitamin D receptor (VDR) is responsible for the initiation of vitamin D signaling cascade. The aim of this study was to assess the associations of VDR genetic variability with PD risk and different PD-related phenotypes. We genotyped 231 well characterized PD patients and 161 healthy blood donors for six VDR single nucleotide polymorphisms, namely rs739837, rs4516035, rs11568820, rs731236, rs2228570, and rs1544410. We observed that VDR rs2228570 is associated with PD risk (p < 0.001). Additionally, we observed associations of specific VDR genotypes with adverse events of dopaminergic treatment. VDR rs1544410 (GG vs. GA + AA: p = 0.005; GG vs. GA: p = 0.009) was associated with the occurrence of visual hallucinations and VDR rs739837 (TT vs. GG: p = 0.036), rs731236 (TT vs. TC + CC: p = 0.011; TT vs. TC: p = 0.028; TT vs. CC: p = 0.035), and rs1544410 (GG vs. GA: p = 0.014) with the occurrence of orthostatic hypotension. We believe that the reported study may support personalized approach to PD treatment, especially in terms of monitoring vitamin D level and vitamin D supplementation in patients with high risk VDR genotypes.

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Section: Discussionsupporting

confidence: 78%

Genetic Variability of the Vitamin D Receptor Affects Susceptibility to Parkinson’s Disease and Dopaminergic Treatment Adverse Events

Redenšek

Kristanc

Blagus

et al. 2022

Front. Aging Neurosci.

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“…In order to test the predictive power of the obtained genetic longevity scores, we performed ROC curve analysis (Fig 4), which showed that all four scores were satisfactory for predicting the possibility of reaching the longevity milestones (90+ and 95+ years) that were above the theoretical cut-off value for this test of 0.5 [35,36]. However, with an AUC score of 0.690, wGLS90 is a more predictive longevity score for survival to the age of 90, and uGLS90 with an AUC score of 0.662 is the less predictive.…”

Section: Plos Onementioning

confidence: 99%

Genetic scores for predicting longevity in the Croatian oldest-old population

et al. 2023

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Longevity is a hallmark of successful ageing and a complex trait with a significant genetic component. In this study, 43 single nucleotide polymorphisms (SNPs) were chosen from the literature and genotyped in a Croatian oldest-old sample (85+ years, sample size (N) = 314), in order to determine whether any of these SNPs have a significant effect on reaching the age thresholds for longevity (90+ years, N = 212) and extreme longevity (95+ years, N = 84). The best models were selected for both survival ages using multivariate logistic regression. In the model for reaching age 90, nine SNPs explained 20% of variance for survival to that age, while the 95-year model included five SNPs accounting for 9.3% of variance. The two SNPs that showed the most significant association (p ≤ 0.01) with longevity were TERC rs16847897 and GHRHR rs2267723. Unweighted and weighted Genetic Longevity Scores (uGLS and wGLS) were calculated and their predictive power was tested. All four scores showed significant correlation with age at death (p ≤ 0.01). They also passed the ROC curve test with at least 50% predictive ability, but wGLS90 stood out as the most accurate score, with a 69% chance of accurately predicting survival to the age of 90.

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“…In summary, PGS may be a useful translational research tool in this arena to test hypotheses about the nature of associations between individual differences in musicality and health conditions, 61,62 with its maximal specificity to identify subsets of patients who may benefit from particular clinical interventions customized to them (e.g., Ref. 63), but PGS is not a tool that can make specific individual determinations.…”

Section: For Common Misconceptions About Heritability)mentioning

confidence: 99%

Confronting ethical and social issues related to the genetics of musicality

Gordon

Martschenko

Nayak

et al. 2023

Annals of the New York Academy of Sciences

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New interdisciplinary research into genetic influences on musicality raises a number of ethical and social issues for future avenues of research and public engagement. The historical intersection of music cognition and eugenics heightens the need to vigilantly weigh potential risks and benefits of these studies and use of their outcomes. Here we bring together diverse perspectives (complex trait genetics, music cognition, musicology, bioethics, and neuroscience) to guide ethical use of this new knowledge. We discuss a framework for incorporating principles of ethically and socially responsible conduct of musicality genetics research into each stage of the research lifecycle: study design, study implementation, potential applications, and communication about the research. MAIN TEXTWith the publication of the first large-scale Genome-wide Association Study (GWAS) of a musicality trait, 1 timely ethical and social considerations require discussion. This recent GWAS of beat synchronization reveals the genetic architecture of the fascinating human tendency to move in time with a musical "beat" (or pulse), a behavior ubiquitous in musical cultures. 2,3 Neurobiological and psychological evidence previously highlighted how beat synchronization is integral to music-making, dancing, singing, within the landscape of musicality as a platform for exploring fundamental mechanisms of sensation, prediction, coordination, and reward. Moreover, music plays a profound social function for humans and there is mounting evidence of

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Polygenic Risk Scores Contribute to Personalized Medicine of Parkinson’s Disease

Cited by 16 publications

References 69 publications

Genetic Variability of the Vitamin D Receptor Affects Susceptibility to Parkinson’s Disease and Dopaminergic Treatment Adverse Events

Genetic Variability of the Vitamin D Receptor Affects Susceptibility to Parkinson’s Disease and Dopaminergic Treatment Adverse Events

Genetic scores for predicting longevity in the Croatian oldest-old population

Confronting ethical and social issues related to the genetics of musicality

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