Parkinson’s disease determinants, prediction and gene-environment interactions in the UK Biobank

Jacobs, Benjamin Meir; Belete, Daniel; Bestwick, Jonathan P.; Blauwendraat, Cornelis; Bandrés‐Ciga, Sara; Heilbron, Karl; Dobson, Ruth; Nalls, Mike A.; Singleton, Andrew B.; Giovannoni, Gavin; Lees, Andrew J.; Schrag, Anette; Noyce, Alastair

doi:10.1101/2020.02.15.950733

Cited by 18 publications

(31 citation statements)

References 45 publications

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“…In our study, family history of PD in a first-or seconddegree relative was associated with fourfold risk, which is higher than reported in the UK Biobank cohort (adjusted OR 2.19 95% CI 1.81-2.65) [52]. Some of the subjects we identified likely carried genetic alterations associated with familial PD, but the likelihood that this is a highly prevalent feature of our population is low given the infrequency of such genetic alterations in the general population.…”

Section: Discussioncontrasting

confidence: 79%

Lifestyle Factors and Parkinson’s Disease Risk in a Rural New England Case-Control Study

Andrew

Anderson

Herrmann

et al. 2021

Parkinson's Disease

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Introduction. Parkinson’s disease (PD) is an age-related neurodegenerative disease likely caused by complex interactions between genetic and environmental risk factors. Exposure to pesticides, toxic metals, solvents, and history of traumatic brain injury have been implicated as environmental risk factors for PD, underscoring the importance of identifying risk factors associated with PD across different communities. Methods. We conducted a questionnaire-based case-control study in a rural area on the New Hampshire/Vermont border, enrolling PD patients and age- and sex-matched controls from the general population between 2017 and 2020. We assessed frequent participation in a variety of recreational and occupational activities and surveyed potential chemical exposures. Results. Suffering from “head trauma or a concussion” prior to diagnosis was associated with a fourfold increased risk of PD. Adjustment for head trauma negated any risk of participation in “strenuous athletic activities.” We observed a 2.7-fold increased risk of PD associated with activities involving lead (adjusted p = 0.038 ). Conclusion. Implicating these factors in PD risk favors public health efforts in exposure mitigation while also motivating future work mechanisms and intervention opportunities.

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Section: Discussioncontrasting

confidence: 79%

Lifestyle Factors and Parkinson’s Disease Risk in a Rural New England Case-Control Study

Andrew

Anderson

Herrmann

et al. 2021

Parkinson's Disease

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“…From the nine studies that defined T2DM as the exposure, 26‐34 the pooled effect estimate was 1.21 (95% CI 1.07–1.36; see Fig. 2).…”

Section: Resultsmentioning

confidence: 99%

Type 2 Diabetes as a Determinant of Parkinson's Disease Risk and Progression

et al. 2021

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A BS TRACT: Background: Type 2 diabetes (T2DM) and Parkinson's disease (PD) are prevalent diseases that affect an aging population. Previous systematic reviews and meta-analyses have explored the relationship between diabetes and the risk of PD, but the results have been conflicting. Objective: The objective was to investigate T2DM as a determinant of PD through a meta-analysis of observational and genetic summary data. Methods: A systematic review and meta-analysis of observational studies was undertaken by searching 6 databases. We selected the highest-quality studies investigating the association of T2DM with PD risk and progression. We then used Mendelian randomization (MR) to investigate the causal effects of genetic liability toward T2DM on PD risk and progression, using summary data derived from genome-wide association studies. Results: In the observational part of the study, pooled effect estimates showed that T2DM was associated with an increased risk of PD (odds ratio [OR] 1.21, 95% confidence interval [CI] 1.07-1.36), and there was some evidence that T2DM was associated with faster progression of motor symptoms (standardized mean difference [SMD] 0.55, 95% CI 0.39-0.72) and cognitive decline (SMD −0.92, 95% CI −1.50 to −0.34). Using MR, we found supportive evidence for a causal effect of diabetes on PD risk (inverse-variance weighted method [IVW] OR 1.08, 95% CI 1.02-1.14; P = 0.010) and some evidence of an effect on motor progression (IVW OR 1.10, 95% CI 1.01-1.20; P = 0.032) but not on cognitive progression. Conclusions: Using meta-analyses of traditional observational studies and genetic data, we observed convincing evidence for an effect of T2DM on PD risk and new evidence to support a role in PD progression.

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“…The association analysis was performed in each cohort assuming an additive genetic model adjusted for sex and the first 4 principal components. 10…”

Section: Courage-pd Projectmentioning

confidence: 99%

Replication of a Novel Parkinson's Locus in a European Ancestry Population

et al. 2021

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Background: A recently published East Asian genome-wide association study of Parkinson;s disease (PD) reported 2 novel risk loci, SV2C and WBSCR17.Objectives: The objective of this study were to determine whether recently reported novel SV2C and WBSCR17 loci contribute to the risk of developing PD in European and East Asian ancestry populations. Methods: We report an association analysis of recently reported variants with PD in the COURAGE-PD cohort (9673 PD patients; 8465 controls) comprising individuals of European and East Asian ancestries. In addition, publicly available summary data (41,386 PD patients; 476,428 controls) were pooled. Results: Our findings confirmed the role of the SV2C variant in PD pathogenesis (rs246814, COURAGE-PD P European = 6.64 × 10 −4 , pooled PD P = 1.15 × 10 −11 ). The WBSCR17 rs9638616 was observed as a significant risk marker in the East Asian pooled population only (P = 1.16 × 10 −8 ). Conclusions: Our comprehensive study provides an up-to-date summary of recently detected novel loci in different PD populations and confirmed the role of SV2C locus as a novel risk factor for PD irrespective of the population or ethnic group analyzed.

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Parkinson’s disease determinants, prediction and gene-environment interactions in the UK Biobank

Abstract: ObjectiveTo systematically investigate the association of environmental risk factors and prodromal features with incident Parkinson's disease (PD) diagnosis and the interaction of genetic risk with these factors. To evaluate existing risk prediction algorithms and the impact of including

Cited by 18 publications

References 45 publications

Lifestyle Factors and Parkinson’s Disease Risk in a Rural New England Case-Control Study

Lifestyle Factors and Parkinson’s Disease Risk in a Rural New England Case-Control Study

Type 2 Diabetes as a Determinant of Parkinson's Disease Risk and Progression

Replication of a Novel Parkinson's Locus in a European Ancestry Population

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