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- Bouyoucef, S E, et al.
(author)
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Poster Session 2 : Monday 4 May 2015, 08
- 2015
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In: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 16 Suppl 1
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Journal article (peer-reviewed)
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| 3. |
- Heckman, Michael G., et al.
(author)
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Population-specific Frequencies for LRRK2 Susceptibility Variants in the Genetic Epidemiology of Parkinson's Disease (GEO-PD) Consortium
- 2013
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In: Movement Disorders. - : Wiley. - 0885-3185. ; 28:12, s. 1740-1744
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Journal article (peer-reviewed)abstract
- BackgroundVariants within the leucine-rich repeat kinase 2 gene are recognized as the most frequent genetic cause of Parkinson's disease. Leucine-rich repeat kinase 2 variation related to disease susceptibility displays many features that reflect the nature of complex, late-onset sporadic disorders like Parkinson's disease. MethodsThe Genetic Epidemiology of Parkinson's Disease Consortium recently performed the largest genetic association study for variants in the leucine-rich repeat kinase 2 gene across 23 different sites in 15 countries. ResultsHerein, we detail the allele frequencies for the novel risk factors (p.A419V and p.M1646T) and the protective haplotype (p.N551K-R1398H-K1423K) nominated in the original publication. Simple population allele frequencies not only can provide insight into the clinical relevance of specific variants but also can help genetically define patient groups. ConclusionsEstablishing individual patient-based genomic susceptibility profiles that incorporate both risk factors and protective factors will determine future diagnostic and treatment strategies. (c) 2013 International Parkinson and Movement Disorder Society
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| 5. |
- Ross, Owen A., et al.
(author)
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Association of LRRK2 exonic variants with susceptibility to Parkinson's disease: a case-control study
- 2011
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In: Lancet Neurology. - 1474-4465. ; 10:10, s. 898-908
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Journal article (peer-reviewed)abstract
- Background The leucine-rich repeat kinase 2 gene (LRRK2) harbours highly penetrant mutations that are linked to familial parkinsonism. However, the extent of its polymorphic variability in relation to risk of Parkinson's disease (PD) has not been assessed systematically. We therefore assessed the frequency of LRRK2 exonic variants in individuals with and without PD, to investigate the role of the variants in PD susceptibility. Methods LRRK2 was genotyped in patients with PD and controls from three series (white, Asian, and Arab-Berber) from sites participating in the Genetic Epidemiology of Parkinson's Disease Consortium. Genotyping was done for exonic variants of LRRK2 that were identified through searches of literature and the personal communications of consortium members. Associations with PD were assessed by use of logistic regression models. For variants that had a minor allele frequency of 0.5% or greater, single variant associations were assessed, whereas for rarer variants information was collapsed across variants. Findings 121 exonic LRRK2 variants were assessed in 15 540 individuals: 6995 white patients with PD and 5595 controls, 1376 Asian patients and 962 controls, and 240 Arab-Berber patients and 372 controls. After exclusion of carriers of known pathogenic mutations, new independent risk associations were identified for polymorphic variants in white individuals (M1646T, odds ratio 1.43, 95% CI 1.15-1.78; p=0.0012) and Asian individuals (A419V, 2.27, 1.35-3.83; p=0.0011). A protective haplotype (N551K-R1398H-K1423K) was noted at a frequency greater than 5% in the white and Asian series, with a similar finding in the Arab-Berber series (combined odds ratio 0.82, 0.72-0.94; p=0.0043). Of the two previously reported Asian risk variants, G2385R was associated with disease (1.73, 1.20-2.49; p=0.0026), but no association was noted for R1628P (0.62, 0.36-1.07; p=0.087). In the Arab-Berber series, Y2189C showed potential evidence of risk association with PD (4.48, 133-15.09; p=0.012). Interpretation The results for LRRK2 show that several rare and common genetic variants in the same gene can have independent effects on disease risk. LRRK2, and the pathway in which it functions, is important in the cause and pathogenesis of PD in a greater proportion of patients with this disease than previously believed. These results will help discriminate those patients who will benefit most from therapies targeted at LRRK2 pathogenic activity. Funding Michael J Fox Foundation and National Institutes of Health.
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| 7. |
- Bergström, L, et al.
(author)
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Colloidal processing of a very fine BaTiO3 powder-effect of particle interactions on the suspension properties, consolidation and sintering behavior
- 1997
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In: Journal of The American Ceramic Society. - 0002-7820 .- 1551-2916. ; 80, s. 291-300
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Journal article (peer-reviewed)abstract
- The relation between the suspension state and the rheological properties, the consolidation, and packing of a very fine (nanosized) BaTiO3 powder has been investigated. The BaTiO3 powder was suspended in a non-aqueous medium by adsorbing fatty acids and a polymeric dispersant, poly(12-hydroxy stearic acid), (PHS), at the BaTiO3/decane interface. Calculated interparticle energies implies that the suspension with PHS adsorbed is colloidally stable while the suspensions with oleic and octanoic acid can be characterised as weakly and strongly flocculated, respectively. Analysis of settling experiments and rheological measurements at high concentrations confirmed this characteristics. Pressure filtration resulted in nearly identical green body densities in spite of the differences in colloidal properties, but the preliminary sintering experiments and microstructural characterisation showed that the strongly flocculated suspension displays a significantly retarded sinterability compared to the colloidally stable and the weakly flocculated suspensions. The absence of a correlation between green density and sintering behavior was explained by considering both the volume taken by the adsorbed fatty acids and the PHS polymer-which can be substantial for nanosized powders- and the state of the suspension. While a decrease in the thickness of adsorbed surfactant or polymer layer will enable a higher particle packing density, such a thin adsorbed layer result in a more strongly flocculated suspension which will resist dense packing. Hence, it is suggested that the green bodies of the colloidally stable and the weakly flocculated suspensions correspond to a relatively homogeneous, but loosely packed, green body microstructure. The strongly flocculated suspension results in a green body with a more inhomogeneous microstructure.
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| 8. |
- Krüger, Rejko, et al.
(author)
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A large-scale genetic association study to evaluate the contribution of Omi/HtrA2 (PARK13) to Parkinson's disease
- 2011
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In: Neurobiology of Aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 32:3, s. 9-548
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Journal article (peer-reviewed)abstract
- High-profile studies have provided conflicting results regarding the involvement of the Omi/HtrA2 gene in Parkinson's disease (PD) susceptibility. Therefore, we performed a large-scale analysis of the association of common Omi/HtrA2 variants in the Genetic Epidemiology of Parkinson's disease (GEO-PD) consortium. GEO-PD sites provided clinical and genetic data including affection status, gender, ethnicity, age at study, age at examination (all subjects); age at onset and family history of PD (patients). Genotyping was performed for the five most informative SNPs spanning the Omi/HtrA2 gene in approximately 2-3 kb intervals (rs10779958, rs2231250, rs72470544, rs1183739, rs2241028). Fixed as well as random effect models were used to provide summary risk estimates of Omi/HtrA2 variants. The 20 GEO-PD sites provided data for 6378 cases and 8880 controls. No overall significant associations for the five Omi/HtrA2 SNPs and PD were observed using either fixed effect or random effect models. The summary odds ratios ranged between 0.98 and 1.08 and the estimates of between-study heterogeneity were not large (non-significant Q statistics for all 5 SNPs; I(2) estimates 0-28%). Trends for association were seen for participants of Scandinavian descent for rs2241028 (OR 1.41, p=0.04) and for rs1183739 for age at examination (cut-off 65 years; OR 1.17, p=0.02), but these would not be significant after adjusting for multiple comparisons and their Bayes factors were only modest. This largest association study performed to define the role of any gene in the pathogenesis of Parkinson's disease revealed no overall strong association of Omi/HtrA2 variants with PD in populations worldwide.
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