Search

Your search keyword '"Gibson, J Mark"' showing total 37 results
Start Over Author "Gibson, J Mark"
37 results on '"Gibson, J Mark"'

1. Association of LRRK2 exonic variants with susceptibility to Parkinson's disease: a case–control study

Author

Ross, Owen A, Soto-Ortolaza, Alexandra I, Heckman, Michael G, Aasly, Jan O, Abahuni, Nadine, Annesi, Grazia, Bacon, Justin A, Bardien, Soraya, Bozi, Maria, Brice, Alexis, Brighina, Laura, Van Broeckhoven, Christine, Carr, Jonathan, Chartier-Harlin, Marie-Christine, Dardiotis, Efthimios, Dickson, Dennis W, Diehl, Nancy N, Elbaz, Alexis, Ferrarese, Carlo, Ferraris, Alessandro, Fiske, Brian, Gibson, J Mark, Gibson, Rachel, Hadjigeorgiou, Georgios M, Hattori, Nobutaka, Ioannidis, John PA, Jasinska-Myga, Barbara, Jeon, Beom S, Kim, Yun Joong, Klein, Christine, Kruger, Rejko, Kyratzi, Elli, Lesage, Suzanne, Lin, Chin-Hsien, Lynch, Timothy, Maraganore, Demetrius M, Mellick, George D, Mutez, Eugénie, Nilsson, Christer, Opala, Grzegorz, Park, Sung Sup, Puschmann, Andreas, Quattrone, Aldo, Sharma, Manu, Silburn, Peter A, Sohn, Young Ho, Stefanis, Leonidas, Tadic, Vera, Theuns, Jessie, Tomiyama, Hiroyuki, Uitti, Ryan J, Valente, Enza Maria, van de Loo, Simone, Vassilatis, Demetrios K, Vilariño-Güell, Carles, White, Linda R, Wirdefeldt, Karin, Wszolek, Zbigniew K, Wu, Ruey-Meei, and Farrer, Matthew J

Published
2011
Full Text
View/download PDF

2. Genetic variation of Omi/HtrA2 and Parkinson's disease

Author

Ross, Owen A., Soto, Alexandra I., Vilariño-Güell, Carles, Heckman, Michael G., Diehl, Nancy N., Hulihan, Mary M., Aasly, Jan O., Sando, Sigrid, Gibson, J. Mark, Lynch, Timothy, Krygowska-Wajs, Anna, Opala, Grzegorz, Barcikowska, Maria, Czyzewski, Krzysztof, Uitti, Ryan J., Wszolek, Zbigniew K., and Farrer, Matthew J.

Published
2008
Full Text
View/download PDF

3. Dopamine β-hydroxylase −1021C>T association and Parkinson's disease

Author

Ross, Owen A., Heckman, Michael G., Soto, Alexandra I., Diehl, Nancy N., Haugarvoll, Kristoffer, Vilariño-Güell, Carles, Aasly, Jan O., Sando, Sigrid, Gibson, J. Mark, Lynch, Timothy, Krygowska-Wajs, Anna, Opala, Grzegorz, Barcikowska, Maria, Czyzewski, Krzysztof, Uitti, Ryan J., Wszolek, Zbigniew K., and Farrer, Matthew J.

Published
2008
Full Text
View/download PDF

6. Identification of a novel LRRK2 mutation linked to autosomal dominant parkinsonism: evidence of a common founder across European populations

Author

Kachergus, Jennifer, Mata, Ignacio F., Hulihan, Mary, Taylor, Julie P., Lincoln, Sarah, Aasly, Jan, Gibson, J. Mark, Ross, Owen A., Lynch Timothy, Wiley, Joseph, Payami, Haydeh, Nutt, John, Maraganore, Demetrius M., Czyzewski, Krzysztof, Styczynska, Maria, Wszolek, Zbigniew K., Farrer, Matthew J., and Toft, Mathias

Subjects
Parkinsonism -- Research, Biological sciences
Published
2005

8. Calbindin-1 association and Parkinsonʼs disease

Author

Soto-Ortolaza, A. I., Behrouz, B., Wider, C., Vilariño-Güell, C., Heckman, M. G., Aasly, J. O., Gibson, J. Mark, Lynch, T., Jasinska-Myga, B., Krygowska-Wajs, A., Opala, G., Barcikowska, M., Czyzewski, K., Uitti, R. J., Wszolek, Z. K., Farrer, M. J., and Ross, O. A.

Published
2010
Full Text
View/download PDF

9. Role of sepiapterin reductase gene at the PARK3 locus in Parkinson's disease

Author

Sharma, Manu, Maraganore, Demetrius M., Ioannidis, John P.A., Riess, Olaf, Aasly, Jan O., Annesi, Grazia, Abahuni, Nadine, Bentivoglio, Anna Rita, Brice, Alexis, Van Broeckhoven, Christine, Chartier-Harlin, Marie-Christine, Destée, Alain, Djarmati, Ana, Elbaz, Alexis, Farrer, Matthew, Ferrarese, Carlo, Gibson, J. Mark, Gispert, Suzana, Hattori, Nobutaka, Jasinska-Myga, Barbara, Klein, Christine, Lesage, Suzanne, Lynch, Timothy, Lichtner, Peter, Lambert, Jean-Charles, Lang, Anthony E., Mellick, George D., De Nigris, Francesa, Opala, Grzegorz, Quattrone, Aldo, Riva, Chiara, Rogaeva, Ekaterina, Ross, Owen A., Satake, Wataru, Silburn, Peter A., Theuns, Jessie, Toda, Tatsushi, Tomiyama, Hiroyuki, Uitti, Ryan J., Wirdefeldt, Karin, Wszolek, Zbigniew, Gasser, Thomas, and Krüger, Rejko

Published
2011
Full Text
View/download PDF

10. A large-scale genetic association study to evaluate the contribution of Omi/HtrA2 (PARK13) to Parkinson's disease

Author

Krüger, Rejko, Sharma, Manu, Riess, Olaf, Gasser, Thomas, Van Broeckhoven, Christine, Theuns, Jessie, Aasly, Jan, Annesi, Grazia, Bentivoglio, Anna Rita, Brice, Alexis, Djarmati, Ana, Elbaz, Alexis, Farrer, Matthew, Ferrarese, Carlo, Gibson, J. Mark, Hadjigeorgiou, Georgios M., Hattori, Nobutaka, Ioannidis, John P.A., Jasinska-Myga, Barbara, Klein, Christine, Lambert, Jean-Charles, Lesage, Suzanne, Lin, Juei-Jueng, Lynch, Timothy, Mellick, George D., de Nigris, Francesa, Opala, Grzegorz, Prigione, Alessandro, Quattrone, Aldo, Ross, Owen A., Satake, Wataru, Silburn, Peter A., Tan, Eng King, Toda, Tatsushi, Tomiyama, Hiroyuki, Wirdefeldt, Karin, Wszolek, Zbigniew, Xiromerisiou, Georgia, and Maraganore, Demetrius M.

Published
2011
Full Text
View/download PDF

11. Independent and joint effects of the MAPT and SNCA genes in Parkinson disease

Author

Elbaz, Alexis, Ross, Owen A, Destée, Alain, Ferrarese, Carlo, Ferraris, Alessandro, Gibson, J Mark, Gispert, Suzana, Hadjigeorgiou, Georgios M, Jasinska-Myga, Barbara, Klein, Christine, Krüger, Rejko, Lambert, Jean-Charles, Ioannidis, John P A, Lohmann, Katja, van de Loo, Simone, Loriot, Marie-Anne, Lynch, Timothy, Mellick, George D, Mutez, Eugénie, Nilsson, Christer, Opala, Grzegorz, Puschmann, Andreas, Quattrone, Aldo, Soto-Ortolaza, Alexandra I, Sharma, Manu, Silburn, Peter A, Stefanis, Leonidas, Uitti, Ryan J, Valente, Enza Maria, Vilariño-Güell, Carles, Wirdefeldt, Karin, Wszolek, Zbigniew K, Xiromerisiou, Georgia, Maraganore, Demetrius M, Moisan, Frédéric, Farrer, Matthew J, Disease, Genetic Epidemiology of Parkinson's, Amouyel, Philippe, Tzourio, Christophe, Mulot, Claire, Bacon, Justin A, Cobb, Stephanie A, Sutherland, Greg T, Siebert, Gerhard A, Dissanayaka, Nadeeka, Aasly, Jan, O'Sullivan, John D, Boyle, Richard S, Pasquier, Florence, Bordet, Régis, Legendre, Jean-Philippe, Auburger, Georg, Hilker, Rüdiger, Abahuni, Nadine, Geisen, Christof, Winkler, Susen, Annesi, Grazia, Gasser, Thomas, Riess, Olaf, Berg, Daniela, Schulte, Claudia, Vassilatis, Demitris, Stamboulis, Eleftherios, Dardiotis, Efthimios, Patramani, Ioanna, Kountra, Persa-Maria, Vogiatzi, Christina, Bozi, Maria, Markou, Katerina, Tarantino, Patrizia, Annesi, Ferdinanda, Bentivoglio, Anna Rita, Guidubaldi, Arianna, Caccialupi, Matilde, De Nigris, Francesca, Riva, Chiara, Pedersen, Nancy L, Nilsson, Karin, Brighina, Laura, Reimer, Jan, Van Gerpen, Jay, Lash, Jennifer, Searcy, Jill, Strongosky, Audrey, Chartier-Harlin, Marie-Christine, Elbaz, A, Ross, O, Ioannidis, J, Soto Ortolaza, A, Moisan, F, Aasly, J, Annesi, G, Bozi, M, Brighina, L, Chartier Harlin, M, Destée, A, Ferrarese, C, Ferraris, A, Gibson, J, Gispert, S, Hadjigeorgiou, G, Jasinska Myga, B, Klein, C, Krüger, R, Lambert, J, Lohmann, K, van de Loo, S, Loriot, M, Lynch, T, Mellick, G, Mutez, E, Nilsson, C, Opala, G, Puschmann, A, Quattrone, A, Sharma, M, Silburn, P, Stefanis, L, Uitti, R, Valente, E, Vilariño Güell, C, Wirdefeldt, K, Wszolek, Z, Xiromerisiou, G, Maraganore, D, and Farrer, M

Subjects
Adult, Male, Parkinson Disease/*genetics, Logistic Model, Polymorphism, Single Nucleotide/*genetics, Single-nucleotide polymorphism, Genome-wide association study, MAPT protein, human, tau Proteins, Biology, alpha-Synuclein/*genetics, Polymorphism, Single Nucleotide, Article, Gene interaction, genetics [Parkinson Disease], Retrospective Studie, Genotype, Odds Ratio, SNP, Humans, genetics, Genetic Predisposition to Disease, ddc:610, SNCA protein, human, Age of Onset, Retrospective Studies, Aged, Genetics, Aged, 80 and over, Haplotype, tau Protein, Parkinson Disease, Middle Aged, genetics [tau Proteins], Settore MED/26 - NEUROLOGIA, Logistic Models, Neurology, Genetic epidemiology, Case-Control Studies, Multiple comparisons problem, genetics [Polymorphism, Single Nucleotide], genetics [alpha-Synuclein], alpha-Synuclein, Female, Neurology (clinical), tau Proteins/*genetics, Case-Control Studie, Human
Abstract

Objective: We studied the independent and joint effects of the genes encoding alpha-synuclein (SNCA) and microtubule-associated protein tau (MAPT) in Parkinson disease (PD) as part of a large meta-analysis of individual data from case-control studies participating in the Genetic Epidemiology of Parkinson's Disease (GEO-PD) consortium. Methods: Participants of Caucasian ancestry were genotyped for a total of 4 SNCA (rs2583988, rs181489, rs356219, rs11931074) and 2 MAPT (rs1052553, rs242557) single nucleotide polymorphism (SNPs). Individual and joint effects of SNCA and MAPT SNPs were investigated using fixed- and random-effects logistic regression models. Interactions were studied on both a multiplicative and an additive scale, and using a case-control and case-only approach. Results: Fifteen GEO-PD sites contributed a total of 5,302 cases and 4,161 controls. All 4 SNCA SNPs and the MAPT H1-haplotype-defining SNP (rs1052553) displayed a highly significant marginal association with PD at the significance level adjusted for multiple comparisons. For SNCA, the strongest associations were observed for SNPs located at the 30 end of the gene. There was no evidence of statistical interaction between any of the 4 SNCA SNPs and rs1052553 or rs242557, neither on the multiplicative nor on the additive scale. Interpretation: This study confirms the association between PD and both SNCA SNPs and the H1 MAPT haplotype. It shows, based on a variety of approaches, that the joint action of variants in these 2 loci is consistent with independent effects of the genes without additional interacting effects. ANN NEUROL 2011; 69: 778-792

Published
2011
Full Text
View/download PDF

12. FGF20 and Parkinson's disease: No evidence of association or pathogenicity via α-synuclein expression

Author

Wider, Christian, Dachsel, Justus C., Soto, Alexandra I., Heckman, Michael G., Diehl, Nancy N., Yue, Mei, Lincoln, Sarah, Aasly, Jan O., Haugarvoll, Kristoffer, Trojanowski, John Q., Papapetropoulos, Spiridon, Mash, Deborah, Rajput, Alex, Rajput, Ali H., Gibson, J. Mark, Lynch, Timothy, Dickson, Dennis W., Uitti, Ryan J., Wszolek, Zbigniew K., Farrer, Matthew J., and Ross, Owen A.

Subjects
Adult, Aged, 80 and over, Fibroblast Growth Factors, Male, alpha-Synuclein, Humans, Female, Parkinson Disease, Middle Aged, Article, Aged
Abstract

Genetic variation in fibroblast growth factor 20 (FGF20) has been associated with risk of Parkinson's disease (PD). Functional evidence suggested the T allele of one SNP, rs12720208 C/T, altered PD risk by increasing FGF20 and alpha-synuclein protein levels. Herein we report our association study of FGF20 and PD risk in four patient-control series (total: 1,262 patients and 1,881 controls), and measurements of FGF20 and alpha-synuclein protein levels in brain samples (nine patients). We found no evidence of association between FGF20 variability and PD risk, and no relationship between the rs12720208 genotype, FGF20 and alpha-synuclein protein levels.

Published
2009

13. Population-specific frequencies for LRRK2 susceptibility variants in the Genetic Epidemiology of Parkinson's Disease (GEO-PD) Consortium.

Author

Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group) [research center], Heckman, Michael G., Soto-Ortolaza, Alexandra I., Aasly, Jan O., Abahuni, Nadine, Annesi, Grazia, Bacon, Justin A., Bardien, Soraya, Bozi, Maria, Brice, Alexis, Brighina, Laura, Carr, Jonathan, Chartier-Harlin, Marie-Christine, Dardiotis, Efthimios, Dickson, Dennis W., Diehl, Nancy N., Elbaz, Alexis, Ferrarese, Carlo, Fiske, Brian, Gibson, J. Mark, Gibson, Rachel, Hadjigeorgiou, Georgios M., Hattori, Nobutaka, Ioannidis, John P. A., Boczarska-Jedynak, Magdalena, Jasinska-Myga, Barbara, Jeon, Beom S., Kim, Yun Joong, Klein, Christine, Krüger, Rejko, Kyratzi, Elli, Lesage, Suzanne, Lin, Chin-Hsien, Lynch, Timothy, Maraganore, Demetrius M., Mellick, George D., Mutez, Eugenie, Nilsson, Christer, Opala, Grzegorz, Park, Sung Sup, Petrucci, Simona, Puschmann, Andreas, Quattrone, Aldo, Sharma, Manu, Silburn, Peter A., Sohn, Young Ho, Stefanis, Leonidas, Tadic, Vera, Theuns, Jessie, Tomiyama, Hiroyuki, Uitti, Ryan J., Valente, Enza Maria, Van Broeckhoven, Christine, van de Loo, Simone, Vassilatis, Demetrios K., Vilarino-Guell, Carles, White, Linda R., Wirdefeldt, Karin, Wszolek, Zbigniew K., Wu, Ruey-Meei, Hentati, Faycal, Farrer, Matthew J., Ross, Owen A., Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group) [research center], Heckman, Michael G., Soto-Ortolaza, Alexandra I., Aasly, Jan O., Abahuni, Nadine, Annesi, Grazia, Bacon, Justin A., Bardien, Soraya, Bozi, Maria, Brice, Alexis, Brighina, Laura, Carr, Jonathan, Chartier-Harlin, Marie-Christine, Dardiotis, Efthimios, Dickson, Dennis W., Diehl, Nancy N., Elbaz, Alexis, Ferrarese, Carlo, Fiske, Brian, Gibson, J. Mark, Gibson, Rachel, Hadjigeorgiou, Georgios M., Hattori, Nobutaka, Ioannidis, John P. A., Boczarska-Jedynak, Magdalena, Jasinska-Myga, Barbara, Jeon, Beom S., Kim, Yun Joong, Klein, Christine, Krüger, Rejko, Kyratzi, Elli, Lesage, Suzanne, Lin, Chin-Hsien, Lynch, Timothy, Maraganore, Demetrius M., Mellick, George D., Mutez, Eugenie, Nilsson, Christer, Opala, Grzegorz, Park, Sung Sup, Petrucci, Simona, Puschmann, Andreas, Quattrone, Aldo, Sharma, Manu, Silburn, Peter A., Sohn, Young Ho, Stefanis, Leonidas, Tadic, Vera, Theuns, Jessie, Tomiyama, Hiroyuki, Uitti, Ryan J., Valente, Enza Maria, Van Broeckhoven, Christine, van de Loo, Simone, Vassilatis, Demetrios K., Vilarino-Guell, Carles, White, Linda R., Wirdefeldt, Karin, Wszolek, Zbigniew K., Wu, Ruey-Meei, Hentati, Faycal, Farrer, Matthew J., and Ross, Owen A.

Abstract

BACKGROUND: Variants 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. METHODS: The 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. RESULTS: Herein, 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. CONCLUSIONS: Establishing individual patient-based genomic susceptibility profiles that incorporate both risk factors and protective factors will determine future diagnostic and treatment strategies.

Published
2013

14. Phactr2 and Parkinson's disease

Author

Wider, Christian, Lincoln, Sarah J., Heckman, Michael G., Diehl, Nancy N., Stone, Jeremy T., Haugarvoll, Kristoffer, Aasly, Jan O., Gibson, J. Mark, Lynch, Timothy, Rajput, Alex, Rajput, Michele L., Uitti, Ryan J., Wszolek, Zbigniew K., Farrer, Matthew J., and Ross, Owen A.

Published
2009
Full Text
View/download PDF

15. Role of sepiapterin reductase gene at the PARK3 locus in Parkinson's disease.

Author

Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group) [research center], Sharma, Manu, Maraganore, Demetrius M., Ioannidis, John P. A., Riess, Olaf, Aasly, Jan O., Annesi, Grazia, Abahuni, Nadine, Bentivoglio, Anna Rita, Brice, Alexis, Van Broeckhoven, Christine, Chartier-Harlin, Marie-Christine, Destee, Alain, Djarmati, Ana, Elbaz, Alexis, Farrer, Matthew, Ferrarese, Carlo, Gibson, J. Mark, Gispert, Suzana, Hattori, Nobutaka, Jasinska-Myga, Barbara, Klein, Christine, Lesage, Suzanne, Lynch, Timothy, Lichtner, Peter, Lambert, Jean-Charles, Lang, Anthony E., Mellick, George D., De Nigris, Francesa, Opala, Grzegorz, Quattrone, Aldo, Riva, Chiara, Rogaeva, Ekaterina, Ross, Owen A., Satake, Wataru, Silburn, Peter A., Theuns, Jessie, Toda, Tatsushi, Tomiyama, Hiroyuki, Uitti, Ryan J., Wirdefeldt, Karin, Wszolek, Zbigniew, Gasser, Thomas, Krüger, Rejko, Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group) [research center], Sharma, Manu, Maraganore, Demetrius M., Ioannidis, John P. A., Riess, Olaf, Aasly, Jan O., Annesi, Grazia, Abahuni, Nadine, Bentivoglio, Anna Rita, Brice, Alexis, Van Broeckhoven, Christine, Chartier-Harlin, Marie-Christine, Destee, Alain, Djarmati, Ana, Elbaz, Alexis, Farrer, Matthew, Ferrarese, Carlo, Gibson, J. Mark, Gispert, Suzana, Hattori, Nobutaka, Jasinska-Myga, Barbara, Klein, Christine, Lesage, Suzanne, Lynch, Timothy, Lichtner, Peter, Lambert, Jean-Charles, Lang, Anthony E., Mellick, George D., De Nigris, Francesa, Opala, Grzegorz, Quattrone, Aldo, Riva, Chiara, Rogaeva, Ekaterina, Ross, Owen A., Satake, Wataru, Silburn, Peter A., Theuns, Jessie, Toda, Tatsushi, Tomiyama, Hiroyuki, Uitti, Ryan J., Wirdefeldt, Karin, Wszolek, Zbigniew, Gasser, Thomas, and Krüger, Rejko

Abstract

Sepiapterin reductase (SPR) gene is an enzyme which catalyses the final step of tetrahydrobiopterin synthesis (BH4) and was implicated in Parkinson's disease (PD) pathogenesis as a candidate gene for PARK3 locus. A number of studies yielded association of the PARK3 locus with PD, and SPR knockout mice were shown to display parkinsonian features. To evaluate the role of SPR gene polymorphisms in diverse populations in PD, we performed collaborative analyses in the Genetic Epidemiology of Parkinson Disease (GEO-PD) Consortium. A total of 5 single nucleotide polymorphisms (3 in the promoter region and 2 in the 3' untranslated region [UTR]) were genotyped. Fixed as well as random effect models were used to provide summary risk estimates of SPR variants. A total of 19 sites provided data for 6547 cases and 9321 controls. Overall odds ratio estimates varied from 0.92 to 1.01. No overall association with the SPR gene using either fixed effect or random effect model was observed in the studied population. I(2) Metric varied from 0% to 36.2%. There was some evidence for an association for participants of North European/Scandinavian descent with the strongest signal for rs1876487 (odds ratio = 0.82; p value = 0.003). Interestingly, families which were used to map the PARK3 locus, have Scandinavian ancestry suggesting a founder effect. In conclusion, this large association study for the SPR gene revealed no association for PD worldwide. However, taking the initial mapping of the PARK3 into account, the role of a population-specific effect warrants consideration in future studies.

Published
2011
Full Text
View/download PDF

16. Association of LRRK2 exonic variants with susceptibility to Parkinson's disease: a case-control study.

Author

Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group) [research center], Ross, Owen A., Soto-Ortolaza, Alexandra I., Heckman, Michael G., Aasly, Jan O., Abahuni, Nadine, Annesi, Grazia, Bacon, Justin A., Bardien, Soraya, Bozi, Maria, Brice, Alexis, Brighina, Laura, Van Broeckhoven, Christine, Carr, Jonathan, Chartier-Harlin, Marie-Christine, Dardiotis, Efthimios, Dickson, Dennis W., Diehl, Nancy N., Elbaz, Alexis, Ferrarese, Carlo, Ferraris, Alessandro, Fiske, Brian, Gibson, J. Mark, Gibson, Rachel, Hadjigeorgiou, Georgios M., Hattori, Nobutaka, Ioannidis, John P. A., Jasinska-Myga, Barbara, Jeon, Beom S., Kim, Yun Joong, Klein, Christine, Krüger, Rejko, Kyratzi, Elli, Lesage, Suzanne, Lin, Chin-Hsien, Lynch, Timothy, Maraganore, Demetrius M., Mellick, George D., Mutez, Eugenie, Nilsson, Christer, Opala, Grzegorz, Park, Sung Sup, Puschmann, Andreas, Quattrone, Aldo, Sharma, Manu, Silburn, Peter A., Sohn, Young Ho, Stefanis, Leonidas, Tadic, Vera, Theuns, Jessie, Tomiyama, Hiroyuki, Uitti, Ryan J., Valente, Enza Maria, van de Loo, Simone, Vassilatis, Demetrios K., Vilarino-Guell, Carles, White, Linda R., Wirdefeldt, Karin, Wszolek, Zbigniew K., Wu, Ruey-Meei, Farrer, Matthew J., Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group) [research center], Ross, Owen A., Soto-Ortolaza, Alexandra I., Heckman, Michael G., Aasly, Jan O., Abahuni, Nadine, Annesi, Grazia, Bacon, Justin A., Bardien, Soraya, Bozi, Maria, Brice, Alexis, Brighina, Laura, Van Broeckhoven, Christine, Carr, Jonathan, Chartier-Harlin, Marie-Christine, Dardiotis, Efthimios, Dickson, Dennis W., Diehl, Nancy N., Elbaz, Alexis, Ferrarese, Carlo, Ferraris, Alessandro, Fiske, Brian, Gibson, J. Mark, Gibson, Rachel, Hadjigeorgiou, Georgios M., Hattori, Nobutaka, Ioannidis, John P. A., Jasinska-Myga, Barbara, Jeon, Beom S., Kim, Yun Joong, Klein, Christine, Krüger, Rejko, Kyratzi, Elli, Lesage, Suzanne, Lin, Chin-Hsien, Lynch, Timothy, Maraganore, Demetrius M., Mellick, George D., Mutez, Eugenie, Nilsson, Christer, Opala, Grzegorz, Park, Sung Sup, Puschmann, Andreas, Quattrone, Aldo, Sharma, Manu, Silburn, Peter A., Sohn, Young Ho, Stefanis, Leonidas, Tadic, Vera, Theuns, Jessie, Tomiyama, Hiroyuki, Uitti, Ryan J., Valente, Enza Maria, van de Loo, Simone, Vassilatis, Demetrios K., Vilarino-Guell, Carles, White, Linda R., Wirdefeldt, Karin, Wszolek, Zbigniew K., Wu, Ruey-Meei, and Farrer, Matthew J.

Abstract

BACKGROUND: 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 associati

Published
2011
Full Text
View/download PDF

17. A large-scale genetic association study to evaluate the contribution of Omi/HtrA2 (PARK13) to Parkinson's disease.

Author

Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group) [research center], Krüger, Rejko, Sharma, Manu, Riess, Olaf, Gasser, Thomas, Van Broeckhoven, Christine, Theuns, Jessie, Aasly, Jan, Annesi, Grazia, Bentivoglio, Anna Rita, Brice, Alexis, Djarmati, Ana, Elbaz, Alexis, Farrer, Matthew, Ferrarese, Carlo, Gibson, J. Mark, Hadjigeorgiou, Georgios M., Hattori, Nobutaka, Ioannidis, John P. A., Jasinska-Myga, Barbara, Klein, Christine, Lambert, Jean-Charles, Lesage, Suzanne, Lin, Juei-Jueng, Lynch, Timothy, Mellick, George D., de Nigris, Francesa, Opala, Grzegorz, Prigione, Alessandro, Quattrone, Aldo, Ross, Owen A., Satake, Wataru, Silburn, Peter A., Tan, Eng King, Toda, Tatsushi, Tomiyama, Hiroyuki, Wirdefeldt, Karin, Wszolek, Zbigniew, Xiromerisiou, Georgia, Maraganore, Demetrius M., Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group) [research center], Krüger, Rejko, Sharma, Manu, Riess, Olaf, Gasser, Thomas, Van Broeckhoven, Christine, Theuns, Jessie, Aasly, Jan, Annesi, Grazia, Bentivoglio, Anna Rita, Brice, Alexis, Djarmati, Ana, Elbaz, Alexis, Farrer, Matthew, Ferrarese, Carlo, Gibson, J. Mark, Hadjigeorgiou, Georgios M., Hattori, Nobutaka, Ioannidis, John P. A., Jasinska-Myga, Barbara, Klein, Christine, Lambert, Jean-Charles, Lesage, Suzanne, Lin, Juei-Jueng, Lynch, Timothy, Mellick, George D., de Nigris, Francesa, Opala, Grzegorz, Prigione, Alessandro, Quattrone, Aldo, Ross, Owen A., Satake, Wataru, Silburn, Peter A., Tan, Eng King, Toda, Tatsushi, Tomiyama, Hiroyuki, Wirdefeldt, Karin, Wszolek, Zbigniew, Xiromerisiou, Georgia, and Maraganore, Demetrius M.

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.

Published
2011
Full Text
View/download PDF

18. Independent and joint effects of the MAPT and SNCA genes in Parkinson disease.

Author

Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group) [research center], Elbaz, Alexis, Ross, Owen A., Ioannidis, John P. A., Soto-Ortolaza, Alexandra I., Moisan, Frederic, Aasly, Jan, Annesi, Grazia, Bozi, Maria, Brighina, Laura, Chartier-Harlin, Marie-Christine, Destee, Alain, Ferrarese, Carlo, Ferraris, Alessandro, Gibson, J. Mark, Gispert, Suzana, Hadjigeorgiou, Georgios M., Jasinska-Myga, Barbara, Klein, Christine, Krüger, Rejko, Lambert, Jean-Charles, Lohmann, Katja, van de Loo, Simone, Loriot, Marie-Anne, Lynch, Timothy, Mellick, George D., Mutez, Eugenie, Nilsson, Christer, Opala, Grzegorz, Puschmann, Andreas, Quattrone, Aldo, Sharma, Manu, Silburn, Peter A., Stefanis, Leonidas, Uitti, Ryan J., Valente, Enza Maria, Vilarino-Guell, Carles, Wirdefeldt, Karin, Wszolek, Zbigniew K., Xiromerisiou, Georgia, Maraganore, Demetrius M., Farrer, Matthew J., Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group) [research center], Elbaz, Alexis, Ross, Owen A., Ioannidis, John P. A., Soto-Ortolaza, Alexandra I., Moisan, Frederic, Aasly, Jan, Annesi, Grazia, Bozi, Maria, Brighina, Laura, Chartier-Harlin, Marie-Christine, Destee, Alain, Ferrarese, Carlo, Ferraris, Alessandro, Gibson, J. Mark, Gispert, Suzana, Hadjigeorgiou, Georgios M., Jasinska-Myga, Barbara, Klein, Christine, Krüger, Rejko, Lambert, Jean-Charles, Lohmann, Katja, van de Loo, Simone, Loriot, Marie-Anne, Lynch, Timothy, Mellick, George D., Mutez, Eugenie, Nilsson, Christer, Opala, Grzegorz, Puschmann, Andreas, Quattrone, Aldo, Sharma, Manu, Silburn, Peter A., Stefanis, Leonidas, Uitti, Ryan J., Valente, Enza Maria, Vilarino-Guell, Carles, Wirdefeldt, Karin, Wszolek, Zbigniew K., Xiromerisiou, Georgia, Maraganore, Demetrius M., and Farrer, Matthew J.

Abstract

OBJECTIVE: We studied the independent and joint effects of the genes encoding alpha-synuclein (SNCA) and microtubule-associated protein tau (MAPT) in Parkinson disease (PD) as part of a large meta-analysis of individual data from case-control studies participating in the Genetic Epidemiology of Parkinson's Disease (GEO-PD) consortium. METHODS: Participants of Caucasian ancestry were genotyped for a total of 4 SNCA (rs2583988, rs181489, rs356219, rs11931074) and 2 MAPT (rs1052553, rs242557) single nucleotide polymorphism (SNPs). Individual and joint effects of SNCA and MAPT SNPs were investigated using fixed- and random-effects logistic regression models. Interactions were studied on both a multiplicative and an additive scale, and using a case-control and case-only approach. RESULTS: Fifteen GEO-PD sites contributed a total of 5,302 cases and 4,161 controls. All 4 SNCA SNPs and the MAPT H1-haplotype-defining SNP (rs1052553) displayed a highly significant marginal association with PD at the significance level adjusted for multiple comparisons. For SNCA, the strongest associations were observed for SNPs located at the 3' end of the gene. There was no evidence of statistical interaction between any of the 4 SNCA SNPs and rs1052553 or rs242557, neither on the multiplicative nor on the additive scale. INTERPRETATION: This study confirms the association between PD and both SNCA SNPs and the H1 MAPT haplotype. It shows, based on a variety of approaches, that the joint action of variants in these 2 loci is consistent with independent effects of the genes without additional interacting effects.

Published
2011

19. Large-scale replication and heterogeneity in Parkinson disease genetic loci

Author

Sharma, Manu, primary, Ioannidis, John P.A., additional, Aasly, Jan O., additional, Annesi, Grazia, additional, Brice, Alexis, additional, Van Broeckhoven, Christine, additional, Bertram, Lars, additional, Bozi, Maria, additional, Crosiers, David, additional, Clarke, Carl, additional, Facheris, Maurizio, additional, Farrer, Matthew, additional, Garraux, Gaetan, additional, Gispert, Suzana, additional, Auburger, Georg, additional, Vilariño-Güell, Carles, additional, Hadjigeorgiou, Georgios M., additional, Hicks, Andrew A., additional, Hattori, Nobutaka, additional, Jeon, Beom, additional, Lesage, Suzanne, additional, Lill, Christina M., additional, Lin, Juei-Jueng, additional, Lynch, Timothy, additional, Lichtner, Peter, additional, Lang, Anthony E., additional, Mok, Vincent, additional, Jasinska-Myga, Barbara, additional, Mellick, George D., additional, Morrison, Karen E., additional, Opala, Grzegorz, additional, Pramstaller, Peter P., additional, Pichler, Irene, additional, Park, Sung Sup, additional, Quattrone, Aldo, additional, Rogaeva, Ekaterina, additional, Ross, Owen A., additional, Stefanis, Leonidas, additional, Stockton, Joanne D., additional, Satake, Wataru, additional, Silburn, Peter A., additional, Theuns, Jessie, additional, Tan, Eng-King, additional, Toda, Tatsushi, additional, Tomiyama, Hiroyuki, additional, Uitti, Ryan J., additional, Wirdefeldt, Karin, additional, Wszolek, Zbigniew, additional, Xiromerisiou, Georgia, additional, Yueh, Kuo-Chu, additional, Zhao, Yi, additional, Gasser, Thomas, additional, Maraganore, Demetrius, additional, Krüger, Rejko, additional, Boyle, R.S, additional, Sellbach, A, additional, O'Sullivan, J.D., additional, Sutherland, G.T., additional, Siebert, G.A, additional, Dissanayaka, N.N.W, additional, Pickut, Barbara, additional, Engelborghs, Sebastiaan, additional, Meeus, Bram, additional, De Deyn, Peter P., additional, Cras, Patrick, additional, Lang, Anthony E, additional, Agid, Y, additional, Anheim, M, additional, Bonnet, A-M, additional, Borg, M, additional, Brice, A, additional, Broussolle, E, additional, Corvol, JC, additional, Damier, P, additional, Destée, A, additional, Dürr, A, additional, Durif, F, additional, Lesage, S, additional, Lohmann, E, additional, Pollak, P, additional, Rascol, O, additional, Tison, F, additional, Tranchant, C, additional, Viallet, F, additional, Vidailhet, M, additional, Tzourio, Christophe, additional, Amouyel, Philippe, additional, Loriot, Marie-Anne, additional, Mutez, Eugénie, additional, Duflot, Aurélie, additional, Legendre, Jean-Philippe, additional, Waucquier, Nawal, additional, Riess, Olaf, additional, Berg, Daniela, additional, Schulte, Claudia, additional, Klein, Christine, additional, Djarmati, Ana, additional, Hagenah, Johann, additional, Lohmann, Katja, additional, Hilker, Rüdiger, additional, van de Loo, Simone, additional, Dardiotis, Efthimios, additional, Tsimourtou, Vaia, additional, Ralli, Styliani, additional, Kountra, Persa, additional, Patramani, Gianna, additional, Vogiatzi, Cristina, additional, Funayama, Manabu, additional, Yoshino, Hiroyo, additional, Li, Yuanzhe, additional, Imamichi, Yoko, additional, Lynch, Tim, additional, Gibson, J. Mark, additional, Valente, Enza Maria, additional, Ferraris, Alessandro, additional, Dallapiccola, Bruno, additional, Ialongo, Tamara, additional, Brighina, Laura, additional, Corradi, Barbara, additional, Piolti, Roberto, additional, Tarantino, Patrizia, additional, Annesi, Ferdinanda, additional, Jeon, Beom S., additional, Park, Sung-Sup, additional, Aasly, J, additional, Klodowska-Duda, Gabriela, additional, Boczarska-Jedynak, Magdalena, additional, Tan, Eng King, additional, Belin, Andrea Carmine, additional, Olson, Lars, additional, Galter, Dagmar, additional, Westerlund, Marie, additional, Sydow, Olof, additional, Nilsson, Christer, additional, Puschmann, Andreas, additional, Lin, JJ, additional, Maraganore, Demetrius M., additional, Ahlskog, J, Eric, additional, de Andrade, Mariza, additional, Lesnick, Timothy G., additional, Rocca, Walter A., additional, Checkoway, Harvey, additional, Ross, Owen A, additional, and Wszolek, Zbigniew K., additional

Published
2012
Full Text
View/download PDF

21. FGF20and Parkinson's disease: No evidence of association or pathogenicity via α-synuclein expression

Author

Wider, Christian, primary, Dachsel, Justus C., additional, Soto, Alexandra I., additional, Heckman, Michael G., additional, Diehl, Nancy N., additional, Yue, Mei, additional, Lincoln, Sarah, additional, Aasly, Jan O., additional, Haugarvoll, Kristoffer, additional, Trojanowski, John Q., additional, Papapetropoulos, Spiridon, additional, Mash, Deborah, additional, Rajput, Alex, additional, Rajput, Ali H., additional, Gibson, J. Mark, additional, Lynch, Timothy, additional, Dickson, Dennis W., additional, Uitti, Ryan J., additional, Wszolek, Zbigniew K., additional, Farrer, Matthew J., additional, and Ross, Owen A., additional

Published
2009
Full Text
View/download PDF

22. Fine-mapping and candidate gene investigation within the PARK10 locus

Author

Haugarvoll, Kristoffer, primary, Toft, Mathias, additional, Skipper, Lisa, additional, Heckman, Michael G, additional, Crook, Julia E, additional, Soto, Alexandra, additional, Ross, Owen A, additional, Hulihan, Mary M, additional, Kachergus, Jennifer M, additional, Sando, Sigrid B, additional, White, Linda R, additional, Lynch, Timothy, additional, Gibson, J Mark, additional, Uitti, Ryan J, additional, Wszolek, Zbigniew K, additional, Aasly, Jan O, additional, and Farrer, Matthew J, additional

Published
2008
Full Text
View/download PDF

23. Pathogenicity of the Lrrk2 R1514Q substitution in Parkinson's disease

Author

Toft, Mathias, primary, Mata, Ignacio F., additional, Ross, Owen A., additional, Kachergus, Jennifer, additional, Hulihan, Mary M., additional, Haugarvoll, Kristoffer, additional, Stone, Jeremy T., additional, Blazquez, Marta, additional, Gibson, J. Mark, additional, Aasly, Jan O., additional, White, Linda R., additional, Lynch, Timothy, additional, Adler, Charles H., additional, Gwinn‐Hardy, Katrina, additional, and Farrer, Matthew J., additional

Published
2007
Full Text
View/download PDF

25. Genomewide Association, Parkinson Disease, and PARK10

Author

Farrer, Matthew J., primary, Haugarvoll, Kristoffer, additional, Ross, Owen A., additional, Stone, Jeremy T., additional, Milkovic, Nicole M., additional, Cobb, Stephanie A., additional, Whittle, Andrew J., additional, Lincoln, Sarah J., additional, Hulihan, Mary M., additional, Heckman, Michael G., additional, White, Linda R., additional, Aasly, Jan O., additional, Gibson, J. Mark, additional, Gosal, David, additional, Lynch, Timothy, additional, Wszolek, Zbigniew K., additional, Uitti, Ryan J., additional, and Toft, Mathias, additional

Published
2006
Full Text
View/download PDF

26. UCHL-1is not a Parkinson's disease susceptibility gene

Author

Healy, Daniel G., primary, Abou-Sleiman, Patrick M., additional, Casas, Juan P., additional, Ahmadi, Kourosh R., additional, Lynch, Timothy, additional, Gandhi, Sonia, additional, Muqit, Miratul M. K., additional, Foltynie, Thomas, additional, Barker, Roger, additional, Bhatia, Kailash P., additional, Quinn, Niall P., additional, Lees, Andrew J., additional, Gibson, J. Mark, additional, Holton, Janice L., additional, Revesz, Tamas, additional, Goldstein, David B., additional, and Wood, Nicholas W., additional

Published
2006
Full Text
View/download PDF

28. A novel polymorphic triplet repeat in intron five of the α-synuclein gene: no evidence of expansion or allelic association with idiopathic Parkinsonʼs disease in the Irish

Author

Ross, Owen A., primary, Awayn, Nuri H., additional, McWhinney, Deborah, additional, Maxwell, Lynn D., additional, El-Agnaf, Omar M. A., additional, Barnett, Yvonne A., additional, Maeve Rea, I., additional, Middleton, Derek, additional, Wallace, Andrew, additional, Gibson, J. Mark, additional, and Curran, Martin D., additional

Published
2002
Full Text
View/download PDF

29. Population-specific frequencies for LRRK2 susceptibility variants in the genetic epidemiology of Parkinson's disease (GEO-PD) consortium.

Author

Heckman, Michael G., Soto‐Ortolaza, Alexandra I., Aasly, Jan O., Abahuni, Nadine, Annesi, Grazia, Bacon, Justin A., Bardien, Soraya, Bozi, Maria, Brice, Alexis, Brighina, Laura, Carr, Jonathan, Chartier‐Harlin, Marie‐Christine, Dardiotis, Efthimios, Dickson, Dennis W., Diehl, Nancy N., Elbaz, Alexis, Ferrarese, Carlo, Fiske, Brian, Gibson, J. Mark, and Gibson, Rachel

Abstract

ABSTRACT Background Variants 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. Methods The 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. Results Herein, 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. Conclusions Establishing individual patient-based genomic susceptibility profiles that incorporate both risk factors and protective factors will determine future diagnostic and treatment strategies. © 2013 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

Published
2013
Full Text
View/download PDF

30. Fine-mapping and candidate gene investigation within the PARK10 locus.

Author

Haugarvoll, Kristoffer, Toft, Mathias, Skipper, Lisa, Heckman, Michael G., Crook, Julia E., Soto, Alexandra, Ross, Owen A., Hulihan, Mary M., Kachergus, Jennifer M., Sando, Sigrid B., White, Linda R., Lynch, Timothy, Gibson, J. Mark, Uitti, Ryan J., Wszolek, Zbigniew K., Aasly, Jan O., and Farrer, Matthew J.

Subjects
CLINICAL trials, GENE mapping, PARKINSON'S disease, NUCLEOTIDES, GENETIC polymorphisms, GENOTYPE-environment interaction
Abstract

Herein, we investigate whether single-nucleotide polymorphisms (SNPs) across the PARK10 locus are associated with susceptibility to Parkinson's disease (PD) or age at onset (AAO) of disease. One hundred and eighty-eight SNPs were genotyped across the PARK10 locus in 180 PD patients and 180 controls from central Norway (stage 1). We then used the linkage disequilibrium (LD) structure from stage 1 to select 75 SNPs for genotyping in 186 patients and 186 controls from Ireland (stage 2). Nineteen SNPs were selected from this and previous studies for follow-up in an extended Norwegian series (530 patients and 1142 controls), the Irish series and a US series (221 patients and 221 controls) (stage 3). After correction for multiple testing, markers within ubiquitin specific peptidase 24 (USP24) are significantly associated with PD within Norwegian, Irish, and US series combined (rs13312: odds ratio (OR) 0.78, P<0.001; rs487230: OR 0.80, P=0.001). Independently, the association for rs13312 is strongest in the extended Norwegian series (OR 0.76, P=0.005), although not significant after correction for multiple testing (P≤0.003 is considered significant). ORs in the Irish series are almost identical, and a similar but a weaker effect was observed for the US series. No marker showed consistent association with AAO. Our data indicate that genetic variability in USP24 is associated with PD. Although our work extends and confirms a previous report, the observed effect size does not explain the PARK10 linkage peak.European Journal of Human Genetics (2009) 17, 336–343; doi:10.1038/ejhg.2008.187; published online 15 October 2008 [ABSTRACT FROM AUTHOR]

Published
2009
Full Text
View/download PDF

31. Ocular fixation instabilities in motor neurone disease.

Author

Donaghy, Colette, Pinnock, Ralph, Abrahams, Sharon, Cardwell, Chris, Hardiman, Orla, Patterson, Victor, McGivern, R. Canice, and Gibson, J. Mark

Subjects
NEUROPSYCHOLOGY research, AMYOTROPHIC lateral sclerosis, VISUAL accommodation, SACCADIC eye movements, CEREBRAL cortex, FRONTAL lobe diseases, NEUROPSYCHOLOGICAL tests
Abstract

Eye movements are classically felt to be spared in motor neurone disease (MND). Although a range of ocular motor disorders have been reported, no consistent pattern has been established. Disturbances of ocular fixation have been noted in MND; however, fixation has not yet been formally examined. With the recent characterization of ocular fixation using saccadic intrusion amplitude and fixation periods, we performed a cross-sectional study to examine for abnormalities of ocular fixation in non-dementing patients with MND. A total of 44 patients and 45 controls were recruited. Fixation was examined using infra-red oculography and all subjects then underwent a neuropsychological evaluation. Saccadic intrusion amplitude was found to be greater in patients compared to controls and in particular, spinal-onset patients. Saccadic intrusion amplitude in patients correlated with neuropsychological measures sensitive to lesions of the frontal lobes. This is the first study to identify abnormalities of fixation in MND and these results indicate that ocular fixation instabilities may be a marker of the sub-clinical frontal lobe dysfunction in MND. A longitudinal study to examine if saccadic intrusion amplitude deteriorates with time would be of interest as this could provide a quantifiable objective marker of disease progression. [ABSTRACT FROM AUTHOR]

Published
2009
Full Text
View/download PDF

32. A novel polymorphic triplet repeat in intron five of the -synuclein gene no evidence of expansion or allelic association with idiopathic Parkinson's disease in the Irish

Author

Ross, Owen A., Awayn, Nuri H., McWhinney, Deborah, Maxwell, Lynn D., El-Agnaf, Omar M. A., Barnett, Yvonne A., Maeve Rea, I., Middleton, Derek, Wallace, Andrew, Gibson, J. Mark, and Curran, Martin D.

Abstract

The recent discovery of two mutations associated with autosomal dominant Parkinson's disease (PD) has led to the hypothesis that the -synuclein gene plays a role in the pathogenesis of PD. Here we report a novel triplet CAA repeat within the unusually large intron 5 sequence of the -synuclein gene. Microsatellite analysis revealed a high degree of polymorphism within the Irish population with seven alleles detected, ranging from eight to 17 CAA repeats. Analysis of the allelegenotype frequency differences observed between an Irish idiopathic PD cohort (n98) and a healthy aged control group (n92) revealed no strong association with either group. All PD subjects displaying homozygous profiles were examined for expansion of the trinucleotide repeat, but no expansion was observed. These results would suggest that polymorphism of the -synuclein gene may not play as significant a role in the pathogenesis of idiopathic PD as previously hypothesised.

Published
2002

33. Large-scale replication and heterogeneity in Parkinson disease genetic loci

Author

Sharma, Manu, Ioannidis, John P A, Facheris, Maurizio, Klein, Christine, Djarmati, Ana, Hagenah, Johann, Lohmann, Katja, Auburger, Georg, Hilker, Rüdiger, van de Loo, Simone, Dardiotis, Efthimios, Tsimourtou, Vaia, Ralli, Styliani, Farrer, Matthew, Kountra, Persa, Patramani, Gianna, Vogiatzi, Cristina, Hattori, Nobutaka, Tomiyama, Hiroyuki, Funayama, Manabu, Yoshino, Hiroyo, Li, Yuanzhe, Imamichi, Yoko, Toda, Tatsushi, Garraux, Gaetan, Satake, Wataru, Lynch, Tim, Gibson, J Mark, Valente, Enza Maria, Ferraris, Alessandro, Dallapiccola, Bruno, Ialongo, Tamara, Brighina, Laura, Corradi, Barbara, Piolti, Roberto, Gispert, Suzana, Tarantino, Patrizia, Annesi, Ferdinanda, Jeon, Beom S, Park, Sung-Sup, Aasly, J., Opala, Grzegorz, Jasinska-Myga, Barbara, Klodowska-Duda, Gabriela, Boczarska-Jedynak, Magdalena, Tan, Eng King, Belin, Andrea Carmine, Olson, Lars, Galter, Dagmar, Westerlund, Marie, Sydow, Olof, Nilsson, Christer, Puschmann, Andreas, Lin, J. J., Maraganore, Demetrius M, Ahlskog, J Eric, Vilariño-Güell, Carles, de Andrade, Mariza, Lesnick, Timothy G, Rocca, Walter A, Checkoway, Harvey, Ross, Owen A, Wszolek, Zbigniew K, Uitti, Ryan J, Hadjigeorgiou, Georgios M, Hicks, Andrew A, Jeon, Beom, Aasly, Jan O, Lesage, Suzanne, Lill, Christina M, Lin, Juei-Jueng, Lynch, Timothy, Lichtner, Peter, Lang, Anthony E, Mok, Vincent, Mellick, George D, Morrison, Karen E, Annesi, Grazia, Pramstaller, Peter P, Pichler, Irene, Park, Sung Sup, Quattrone, Aldo, Rogaeva, Ekaterina, Stefanis, Leonidas, Stockton, Joanne D, Brice, Alexis, Silburn, Peter A, Theuns, Jessie, Tan, Eng-King, Wirdefeldt, Karin, Wszolek, Zbigniew, Xiromerisiou, Georgia, Yueh, Kuo-Chu, Van Broeckhoven, Christine, Zhao, Yi, Gasser, Thomas, Maraganore, Demetrius, Krüger, Rejko, Consortium, GEO-PD, Boyle, R. S., Sellbach, A., O'Sullivan, J. D., Sutherland, G. T., Siebert, G. A., Bertram, Lars, Dissanayaka, N. N. W., Crosiers, David, Pickut, Barbara, Engelborghs, Sebastiaan, Meeus, Bram, De Deyn, Peter P, Cras, Patrick, Bozi, Maria, Agid, Y., Anheim, M., Bonnet, A-M, Borg, M., Brice, A., Broussolle, E., Corvol, J. C., Damier, P., Destée, A., Dürr, A., Durif, F., Lesage, S., Lohmann, E., Pollak, P., Rascol, O., Tison, F., Tranchant, C., Viallet, F., Vidailhet, M., Clarke, Carl, Tzourio, Christophe, Amouyel, Philippe, Loriot, Marie-Anne, Mutez, Eugénie, Duflot, Aurélie, Legendre, Jean-Philippe, Waucquier, Nawal, Riess, Olaf, Berg, Daniela, Schulte, Claudia, Pathologic Biochemistry and Physiology, Pollak, Pierre, De Deyn, Peter Paul, and GEO-PD Consortium

Subjects
Male, Genotype, Single-nucleotide polymorphism, Genome-wide association study, Case-control studies, Biology, Polymorphism, Single Nucleotide, Gene Frequency, genetics [Parkinson Disease], Humans, Genetic Predisposition to Disease, ddc:610, Allele, Parkinson Disease/genetics, Allele frequency, Alleles, Genetic association, Aged, Genetics, Medicine(all), Case-control study, Parkinson Disease, Odds ratio, Middle Aged, ddc:616.8, Genetic epidemiology, Genetic Loci, Case-Control Studies, Female, Neurology (clinical), Human medicine, Genome-Wide Association Study
Abstract

Objective: Eleven genetic loci have reached genome-wide significance in a recent meta-analysis of genome-wide association studies in Parkinson disease (PD) based on populations of Caucasian descent. The extent to which these genetic effects are consistent across different populations is unknown. Methods: Investigators from the Genetic Epidemiology of Parkinson9s Disease Consortium were invited to participate in the study. A total of 11 SNPs were genotyped in 8,750 cases and 8,955 controls. Fixed as well as random effects models were used to provide the summary risk estimates for these variants. We evaluated between-study heterogeneity and heterogeneity between populations of different ancestry. Results: In the overall analysis, single nucleotide polymorphisms (SNPs) in 9 loci showed significant associations with protective per-allele odds ratios of 0.78–0.87 ( LAMP3 , BST1 , and MAPT ) and susceptibility per-allele odds ratios of 1.14–1.43 ( STK39 , GAK , SNCA , LRRK2 , SYT11 , and HIP1R ). For 5 of the 9 replicated SNPs there was nominally significant between-site heterogeneity in the effect sizes ( I 2 estimates ranged from 39% to 48%). Subgroup analysis by ethnicity showed significantly stronger effects for the BST1 (rs11724635) in Asian vs Caucasian populations and similar effects for SNCA , LRRK2 , LAMP3 , HIP1R , and STK39 in Asian and Caucasian populations, while MAPT rs2942168 and SYT11 rs34372695 were monomorphic in the Asian population, highlighting the role of population-specific heterogeneity in PD. Conclusion: Our study allows insight to understand the distribution of newly identified genetic factors contributing to PD and shows that large-scale evaluation in diverse populations is important to understand the role of population-specific heterogeneity. Neurology ® 2012;79:659–667

Full Text
View/download PDF

34. Functional promoter region polymorphism of the proinflammatory chemokine IL-8 gene associates with Parkinson's disease in the Irish

Author

Ross, Owen A., O'Neill, Claire, Rea, I. Maeve, Lynch, Tim, Gosal, David, Wallace, Andrew, Curran, Martin D., Middleton, Derek, and Gibson, J. Mark

Subjects
*GENETIC polymorphisms, *CHEMOKINES, *INFLAMMATORY mediators, *PARKINSON'S disease
Abstract

Parkinson''s disease (PD) is one of the most prevalent neurodegenerative disorders and is characterized by the progressive loss of dopamine neurons in the substantia nigra. There is increasing evidence to suggest the inflammatory response of the brain contributes to the pathogenesis of PD. This study investigated the frequency of polymorphism located in the critical promoter region of the proinflammatory cytokine genes: interleukin (IL)–2, IL-6, IL-8, and tumor necrosis factor alpha (TNF-α) within a cohort of patients with PD in comparison to a group of healthy elderly individuals. No association was observed for single nucleotide polymorphism in the promoter regions of the IL-2, IL-6, and TNF-α genes. The single nucleotide polymorphism in the chemokine IL-8 gene was observed to associate with PD and appeared to be independent of age at onset. This association further supports the theory that the proinflammatory response in the brains of patients with PD plays a role in the pathogenesis of the disease and warrants further investigation into the role of chemokines in the brain, and a more detailed analysis of the genetics involved in the immune response of the brain. [Copyright &y& Elsevier]

Published
2004
Full Text
View/download PDF

35. UCHL-1 is not a Parkinson's disease susceptibility gene.

Author

Healy DG, Abou-Sleiman PM, Casas JP, Ahmadi KR, Lynch T, Gandhi S, Muqit MM, Foltynie T, Barker R, Bhatia KP, Quinn NP, Lees AJ, Gibson JM, Holton JL, Revesz T, Goldstein DB, and Wood NW

Subjects
Case-Control Studies, Confidence Intervals, Female, Genotype, Humans, Male, Meta-Analysis as Topic, Middle Aged, Odds Ratio, Serine genetics, Tyrosine genetics, Linkage Disequilibrium, Parkinson Disease genetics, Polymorphism, Genetic, Ubiquitin Thiolesterase genetics
Abstract

Objective: The UCHL-1 gene is widely cited as a susceptibility factor for sporadic Parkinson's disease (PD). The strongest evidence comes from a meta-analysis of small studies that reported the S18Y polymorphism as protective against PD, after pooling studies of white and Asian subjects. Here, we present data that challenge this association., Methods: In a new large case-control study in white individuals (3,023 subjects), the S18Y variant was not protective against PD under any genetic model of inheritance. Similarly, a more powerful haplotype-tagging approach did not detect other associated variants., Results: Finally, in an updated S18Y-PD meta-analysis (6,594 subjects), no significant association was observed under additive, recessive, or dominant models (odds ratio = 1.00 [95% confidence interval: 0.74-1.33]; odds ratio = 1.01 [95% confidence interval: 0.76-1.35]; and odds ratio = 0.96 [95% confidence interval: 0.86-1.08], respectively), and a cumulative meta-analysis showed a trend toward a null effect., Interpretation: Based on the current evidence, the UCHL-1 gene does not exhibit a protective effect in PD.

Published
2006
Full Text
View/download PDF

36. mt4216C variant in linkage with the mtDNA TJ cluster may confer a susceptibility to mitochondrial dysfunction resulting in an increased risk of Parkinson's disease in the Irish.

Author

Ross OA, McCormack R, Maxwell LD, Duguid RA, Quinn DJ, Barnett YA, Rea IM, El-Agnaf OM, Gibson JM, Wallace A, Middleton D, and Curran MD

Subjects
Adult, Aged, Aged, 80 and over, Case-Control Studies, Female, Genetic Predisposition to Disease, Haplotypes, Humans, Ireland, Longevity, Male, Middle Aged, Parkinson Disease metabolism, Point Mutation, Polymorphism, Restriction Fragment Length, DNA, Mitochondrial genetics, Genetic Linkage, Parkinson Disease genetics, Polymorphism, Genetic
Abstract

Polymorphism of the mtDNA genome has been implicated as playing a role in the development and pathogenesis of Parkinson's disease (PD). A PCR-RFLP methodology was employed to generate genetic haplotypes for a cohort of 90 PD sufferers. No association was observed between the various mtDNA haplotypes observed and PD in comparison to healthy aged controls. The longevity-associated European J haplogroup and T haplogroup were identified and were both found to be in tight linkage with the mt4216C polymorphism. The mt4216C variant was observed at a significantly increased frequency in the PD cases (28%) in comparison to the healthy aged controls (15%; p=0.014). However, when the frequency of the mt4216C variant was examined in a cohort of 200 young controls (18-45 years) a similar frequency to the PD cases (25%) was observed. The frequencies obtained for the two branches of the J haplogroup (J1 and J2) and the T haplogroup in the cohort of PD subjects also reflected those observed for the young controls used in the previous longevity study. These findings lead one to postulate that the mt4216C variant, in linkage with the mtDNA TJ cluster, may influence mitochondrial dysfunction, resulting in an increased risk of PD.

Published
2003
Full Text
View/download PDF

37. A novel polymorphic triplet repeat in intron five of the alpha-synuclein gene: no evidence of expansion or allelic association with idiopathic Parkinson's disease in the Irish.

Author

Ross OA, Awayn NH, McWhinney D, Maxwell LD, El-Agnaf OM, Barnett YA, Rea IM, Middleton D, Wallace A, Gibson JM, and Curran MD

Subjects
Adult, Aged, Aged, 80 and over, Base Sequence genetics, Chromosomes, Human, Pair 4 genetics, DNA Mutational Analysis, Female, Genetic Testing, Humans, Introns genetics, Ireland ethnology, Male, Microsatellite Repeats genetics, Middle Aged, Molecular Sequence Data, Synucleins, alpha-Synuclein, Brain Chemistry genetics, Gene Frequency genetics, Nerve Tissue Proteins genetics, Parkinson Disease genetics, Polymorphism, Genetic genetics, Trinucleotide Repeat Expansion genetics, Trinucleotide Repeats genetics
Abstract

The recent discovery of two mutations associated with autosomal dominant Parkinson's disease (PD) has led to the hypothesis that the alpha-synuclein gene plays a role in the pathogenesis of PD. Here we report a novel triplet CAA repeat within the unusually large intron 5 sequence of the alpha-synuclein gene. Microsatellite analysis revealed a high degree of polymorphism within the Irish population with seven alleles detected, ranging from eight to 17 CAA repeats. Analysis of the allele/genotype frequency differences observed between an Irish idiopathic PD cohort (eta = 98) and a healthy aged control group ( eta= 92) revealed no strong association with either group. All PD subjects displaying homozygous profiles were examined for expansion of the trinucleotide repeat, but no expansion was observed. These results would suggest that polymorphism of the alpha-synuclein gene may not play as significant a role in the pathogenesis of idiopathic PD as previously hypothesised.

Published
2002
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results