Independent and Joint Effects of the MAPT and SNCA Genes in Parkinson Disease

Alexis Elbaz; Owen A. Ross; John P. A. Ioannidis; Alexandra I. Soto-Ortolaza; Frederic Moisan; Jan Aasly; Grazia Annesi; Maria Bozi; Laura Brighina; Marie-Christine Chartier-Harlin; Alain Destee; Carlo Ferrarese; Alessandro Ferraris; J. Mark Gibson; Suzana Gispert; Georgios M. Hadjigeorgiou; Barbara Jasinska-Myga; Christine Klein; Rejko Krueger; Jean-Charles Lambert; Katja Lohmann; Simone van de Loo; Marie-Anne Loriot; Timothy Lynch; George D. Mellick; Eugenie Mutez; Christer Nilsson; Grzegorz Opala; Andreas Puschmann; Aldo Quattrone; Manu Sharma; Peter A. Silburn; Leonidas Stefanis; Ryan J. Uitti; Enza Maria Valente; Carles Vilarino-Gueell; Karin Wirdefeldt; Zbigniew K. Wszolek; Georgia Xiromerisiou; Demetrius M. Maraganore; Matthew J. Farrer

doi:10.1002/ana.22321

Independent and Joint Effects of the MAPT and SNCA Genes in Parkinson Disease

Alexis Elbaz, Owen A. Ross, John P. A. Ioannidis, Alexandra I. Soto-Ortolaza, Frederic Moisan, Jan Aasly, Grazia Annesi, Maria Bozi, Laura Brighina, Marie-Christine Chartier-Harlin, Alain Destee, Carlo Ferrarese, Alessandro Ferraris, J. Mark Gibson, Suzana Gispert, Georgios M. Hadjigeorgiou, Barbara Jasinska-Myga, Christine Klein, Rejko Krueger, Jean-Charles LambertKatja Lohmann, Simone van de Loo, Marie-Anne Loriot, Timothy Lynch, George D. Mellick, Eugenie Mutez, Christer Nilsson, Grzegorz Opala, Andreas Puschmann, Aldo Quattrone, Manu Sharma, Peter A. Silburn, Leonidas Stefanis, Ryan J. Uitti, Enza Maria Valente, Carles Vilarino-Gueell, Karin Wirdefeldt, Zbigniew K. Wszolek, Georgia Xiromerisiou, Demetrius M. Maraganore, Matthew J. Farrer

Research output: Contribution to journal › Article › peer-review

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

Original language	English
Pages (from-to)	778-792
Journal	Annals of Neurology
Volume	69
Issue number	5
DOIs	https://doi.org/10.1002/ana.22321
Publication status	Published - 2011

Bibliographical note

The information about affiliations in this record was updated in December 2015.
The record was previously connected to the following departments: Department of Psychogeriatrics (013304000), Neurology, Lund (013027000)

Subject classification (UKÄ)

Geriatrics
Psychiatry
Neurology

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10.1002/ana.22321

1 Doctoral Thesis (compilation)

Heredity in Parkinson's disease. From rare mutations to common genetic risk factors.
Puschmann, A., 2011, Lund University. 174 p.
Research output: Thesis › Doctoral Thesis (compilation)

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Elbaz, A., Ross, O. A., Ioannidis, J. P. A., Soto-Ortolaza, A. I., Moisan, F., Aasly, J., Annesi, G., Bozi, M., Brighina, L., Chartier-Harlin, M.-C., Destee, A., Ferrarese, C., Ferraris, A., Gibson, J. M., Gispert, S., Hadjigeorgiou, G. M., Jasinska-Myga, B., Klein, C., Krueger, R., ... Farrer, M. J. (2011). Independent and Joint Effects of the MAPT and SNCA Genes in Parkinson Disease. Annals of Neurology, 69(5), 778-792. https://doi.org/10.1002/ana.22321

@article{8878d8200fee4bdf808bb2df4d597a7d,

title = "Independent and Joint Effects of the MAPT and SNCA Genes in Parkinson Disease",

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",

author = "Alexis Elbaz and Ross, {Owen A.} and Ioannidis, {John P. A.} and Soto-Ortolaza, {Alexandra I.} and Frederic Moisan and Jan Aasly and Grazia Annesi and Maria Bozi and Laura Brighina and Marie-Christine Chartier-Harlin and Alain Destee and Carlo Ferrarese and Alessandro Ferraris and Gibson, {J. Mark} and Suzana Gispert and Hadjigeorgiou, {Georgios M.} and Barbara Jasinska-Myga and Christine Klein and Rejko Krueger and Jean-Charles Lambert and Katja Lohmann and {van de Loo}, Simone and Marie-Anne Loriot and Timothy Lynch and Mellick, {George D.} and Eugenie Mutez and Christer Nilsson and Grzegorz Opala and Andreas Puschmann and Aldo Quattrone and Manu Sharma and Silburn, {Peter A.} and Leonidas Stefanis and Uitti, {Ryan J.} and Valente, {Enza Maria} and Carles Vilarino-Gueell and Karin Wirdefeldt and Wszolek, {Zbigniew K.} and Georgia Xiromerisiou and Maraganore, {Demetrius M.} and Farrer, {Matthew J.}",

note = "The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Department of Psychogeriatrics (013304000), Neurology, Lund (013027000)",

year = "2011",

doi = "10.1002/ana.22321",

language = "English",

volume = "69",

pages = "778--792",

journal = "Annals of Neurology",

issn = "1531-8249",

publisher = "John Wiley & Sons Inc.",

number = "5",

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Elbaz, A, Ross, OA, Ioannidis, JPA, Soto-Ortolaza, AI, Moisan, F, Aasly, J, Annesi, G, Bozi, M, Brighina, L, Chartier-Harlin, M-C, Destee, A, Ferrarese, C, Ferraris, A, Gibson, JM, Gispert, S, Hadjigeorgiou, GM, Jasinska-Myga, B, Klein, C, Krueger, R, Lambert, J-C, Lohmann, K, van de Loo, S, Loriot, M-A, Lynch, T, Mellick, GD, Mutez, E, Nilsson, C, Opala, G, Puschmann, A, Quattrone, A, Sharma, M, Silburn, PA, Stefanis, L, Uitti, RJ, Valente, EM, Vilarino-Gueell, C, Wirdefeldt, K, Wszolek, ZK, Xiromerisiou, G, Maraganore, DM & Farrer, MJ 2011, 'Independent and Joint Effects of the MAPT and SNCA Genes in Parkinson Disease', Annals of Neurology, vol. 69, no. 5, pp. 778-792. https://doi.org/10.1002/ana.22321

TY - JOUR

T1 - Independent and Joint Effects of the MAPT and SNCA Genes in Parkinson Disease

AU - Elbaz, Alexis

AU - Ross, Owen A.

AU - Ioannidis, John P. A.

AU - Soto-Ortolaza, Alexandra I.

AU - Moisan, Frederic

AU - Aasly, Jan

AU - Annesi, Grazia

AU - Bozi, Maria

AU - Brighina, Laura

AU - Chartier-Harlin, Marie-Christine

AU - Destee, Alain

AU - Ferrarese, Carlo

AU - Ferraris, Alessandro

AU - Gibson, J. Mark

AU - Gispert, Suzana

AU - Hadjigeorgiou, Georgios M.

AU - Jasinska-Myga, Barbara

AU - Klein, Christine

AU - Krueger, Rejko

AU - Lambert, Jean-Charles

AU - Lohmann, Katja

AU - van de Loo, Simone

AU - Loriot, Marie-Anne

AU - Lynch, Timothy

AU - Mellick, George D.

AU - Mutez, Eugenie

AU - Nilsson, Christer

AU - Opala, Grzegorz

AU - Puschmann, Andreas

AU - Quattrone, Aldo

AU - Sharma, Manu

AU - Silburn, Peter A.

AU - Stefanis, Leonidas

AU - Uitti, Ryan J.

AU - Valente, Enza Maria

AU - Vilarino-Gueell, Carles

AU - Wirdefeldt, Karin

AU - Wszolek, Zbigniew K.

AU - Xiromerisiou, Georgia

AU - Maraganore, Demetrius M.

AU - Farrer, Matthew J.

N1 - The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Department of Psychogeriatrics (013304000), Neurology, Lund (013027000)

PY - 2011

Y1 - 2011

N2 - 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

AB - 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

U2 - 10.1002/ana.22321

DO - 10.1002/ana.22321

M3 - Article

SN - 1531-8249

VL - 69

SP - 778

EP - 792

JO - Annals of Neurology

JF - Annals of Neurology

IS - 5

ER -

Independent and Joint Effects of the MAPT and SNCA Genes in Parkinson Disease

Abstract

Bibliographical note

Subject classification (UKÄ)

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Research output

Heredity in Parkinson's disease. From rare mutations to common genetic risk factors.

Cite this