Familial aggregation of Parkinson's disease may affect progression of motor symptoms and dementia

Gaare, Johannes Jernqvist; Skeie, Geir; Tzoulis, Charalampos; Larsen, Jan Petter; Tysnes, Ole‐Bjørn

doi:10.1002/mds.26856

Cited by 12 publications

(11 citation statements)

References 25 publications

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“…Consequently, 1 or more unknown mechanisms must be responsible for the observed association between family history and later age at onset. The previous report showing slower progression in familial cases is consistent with the notion of familial PD as paradoxically milder than what should be expected based on the genetic load …”

Section: Relationship Between Genetic Risk Age At Onset and Family supporting

confidence: 86%

“…Presuming that common risk loci contribute to familial clustering in non‐Mendelian PD, one would expect cumulative genetic risk score (GRS) to be on average higher in patients with a positive family history. However, a recent study reported slower progression in patients with affected first‐degree relatives …”

Section: Relationship Between Genetic Risk Age At Onset and Family mentioning

confidence: 95%

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A paradoxical relationship between family history, onset age, and genetic risk in Parkinson's disease

et al. 2018

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Section: Relationship Between Genetic Risk Age At Onset and Family supporting

confidence: 86%

Section: Relationship Between Genetic Risk Age At Onset and Family mentioning

confidence: 95%

A paradoxical relationship between family history, onset age, and genetic risk in Parkinson's disease

et al. 2018

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“…A recent population-based study using family history questionnaires found that the first-degree relatives of patients with PD had a higher risk of developing PD (RR: 1.988, p =0.036), which was more in line with our result. 25 However, our estimate of heritability having only 11.0% of the accountability for PD in the Taiwanese population is relatively low compared with previous estimations made from genome-wide association analyses in European cohorts. 7 , 26 This difference might be ascribed to differences in study populations and estimation methods.…”

Section: Discussioncontrasting

confidence: 66%

Familial aggregation of Parkinson’s disease and coaggregation with neuropsychiatric diseases: a population-based cohort study

Liu

Lin

Kuo

et al. 2018

CLEP

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BackgroundIndividuals with a family history of Parkinson’s disease (PD) appear to have a higher risk of developing PD and other neuropsychiatric diseases. However, estimates of the relative risks (RRs) of PD and the roles of genetic and environmental factors in PD susceptibility are unclear. The aim of this study was to examine familial aggregation and genetic contributions to PD and the RRs of other neuropsychiatric diseases in relatives of PD patients.MethodsIn this population-based family cohort study, the records of all individuals actively registered in the Taiwan National Health Insurance Research Database in 2015 were queried (N=24,349,599). In total, 149,187 individuals with a PD-affected parent, 3,698 with an affected offspring, 3,495 with an affected sibling, and 15 with an affected twin were identified. Diagnoses of PD were ascertained between January 1, 1999, and December 31, 2015. The prevalence and RRs of PD and other neuropsychiatric diseases in individuals with first-degree relatives with PD, as well as the contributions of heritability and environmental factors to PD susceptibility were investigated.ResultsThe prevalence of PD was 0.46% in the general population and 0.52% in individuals with first-degree relatives with PD. The RR (95% CI) for PD was 2.20 (1.41–3.45) for siblings, 1.59 (1.47–1.73) for parents, 1.86 (1.63–2.11) for offspring, 63.12 (16.45–242.16) for twins, and 1.46 (1.41–1.52) for spouses. The RR (95% CI) in individuals with first-degree relatives with PD was 1.66 (1.57–1.76) for essential tremor, 1.68 (1.61–1.75) for schizophrenia, and 1.20 (1.12–1.28) for Alzheimer’s disease. The estimated contribution to the phenotypic variance of PD was 11.0% for heritability, 9.1% for shared environmental factors, and 79.9% for non-shared environmental factors.ConclusionFirst-degree relatives of PD patients are more likely to develop PD and other neuropsychiatric diseases. Environmental factors account for a high proportion of the phenotypic variance of PD.

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“…20,21 While in many cases dimerization 10,11 and in general molecular complexes formation 22,23 are essential and required events for normal function of the cell, non-natural aggregation is typically unwanted phenomena and is frequently associated with diseases. 24,25 In colloid science, aggregation is typically an unwanted effect and care must be taken to prevent that. For this purpose, the electrostatic potential around macromolecules is attributed to two quantities: electrophoretic mobility (μ) and zeta-potential (ζ-potential).…”

Section: ■ Introductionmentioning

confidence: 99%

A New DelPhi Feature for Modeling Electrostatic Potential around Proteins: Role of Bound Ions and Implications for Zeta-Potential

Chakravorty

Jia

et al. 2017

Langmuir

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A new feature of the popular software DelPhi is developed and reported, allowing for computing the surface averaged electrostatic potential (SAEP) of macromolecules. The user is given the option to specify the distance from the van der Waals surface where the electrostatic potential will be outputted. In conjunction with DelPhiPKa and the BION server, the user can adjust the charges of titratable groups according to specific pH values, and add explicit ions bound to the macromolecular surface. This approach is applied to a set of four proteins with "experimentally" delivered zeta (ζ)-potentials at different pH values and salt concentrations. It has been demonstrated that the protocol is capable of predicting ζ-potentials in the case of proteins with relatively large net charges. This protocol has been less successful for proteins with low net charges. The work demonstrates that in the case of proteins with large net charges, the electrostatic potential should be collected at distances about 4 Å away from the vdW surface and explicit ions should be added at a binding energy cutoff larger than 1-2kT, in order to accurately predict ζ-potentials. The low salt conditions substantiate this effect of ions on SAEP.

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Familial aggregation of Parkinson's disease may affect progression of motor symptoms and dementia

Cited by 12 publications

References 25 publications

A paradoxical relationship between family history, onset age, and genetic risk in Parkinson's disease

A paradoxical relationship between family history, onset age, and genetic risk in Parkinson's disease

Familial aggregation of Parkinson’s disease and coaggregation with neuropsychiatric diseases: a population-based cohort study

A New DelPhi Feature for Modeling Electrostatic Potential around Proteins: Role of Bound Ions and Implications for Zeta-Potential

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Familial aggregation of Parkinson's disease may affect progression of motor symptoms and dementia

Cited by 12 publications

References 25 publications

A paradoxical relationship between family history, onset age, and genetic risk in Parkinson's disease

A paradoxical relationship between family history, onset age, and genetic risk in Parkinson's disease

Familial aggregation of Parkinson&rsquo;s disease and coaggregation with neuropsychiatric diseases: a population-based cohort study

A New DelPhi Feature for Modeling Electrostatic Potential around Proteins: Role of Bound Ions and Implications for Zeta-Potential

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Familial aggregation of Parkinson’s disease and coaggregation with neuropsychiatric diseases: a population-based cohort study