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

A Elbaz; Oa Ross; Jp Ioannidis; Ai Soto Ortolaza; J Aasly; M Bozi; Mc Chartier Harlin; A Destée; C Ferrarese; A Ferraris; Jm Gibson; Gm Hadjigeorgiou; B Jasinska Myga; Krüger R Klein C; K Lohmann; Ma Loriot; Gd Mellick; E Mutez; C Nilsson; A Puschmann; A Quattrone; M Sharma; Pa Silburn; L Stefanis; Em Valente; C Vilariño Güell; K Wirdefeldt; Zk Wszolek; G Xiromerisiou; Mj Farrer; P Amouyel; C Tzourio; C Mulot; Ja Bacon; Sa Cobb; Gt Sutherland; Ga Siebert; N Dissanayaka; Jd O'Sullivan; Rs Boyle; R Bordet; Jp Legendre; G Auburger; N Abahuni; S Winkler; T Gasser; O Riess; D Berg; C Schulte; D Vassilatis; E Stamboulis; E Dardiotis; I Patramani; Pm Kountra; C Vogiatzi; K Markou; P Tarantino; F Annesi; Anna Rita Bentivoglio; Arianna Guidubaldi; M Caccialupi; Francesca De Nigris; Nl Pedersen; J Reimer; J Lash; J Searcy; A. Strongosky

doi:10.1002/ana.22321

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

A Elbaz, Oa Ross, Jp Ioannidis, Ai Soto Ortolaza, J Aasly, M Bozi, Mc Chartier Harlin, A Destée, C Ferrarese, A Ferraris, Jm Gibson, Gm Hadjigeorgiou, B Jasinska Myga, Krüger R Klein C, K Lohmann, Ma Loriot, Gd Mellick, E Mutez, C Nilsson, A PuschmannA Quattrone, M Sharma, Pa Silburn, L Stefanis, Em Valente, C Vilariño Güell, K Wirdefeldt, Zk Wszolek, G Xiromerisiou, Mj Farrer, P Amouyel, C Tzourio, C Mulot, Ja Bacon, Sa Cobb, Gt Sutherland, Ga Siebert, N Dissanayaka, Jd O'Sullivan, Rs Boyle, R Bordet, Jp Legendre, G Auburger, N Abahuni, S Winkler, T Gasser, O Riess, D Berg, C Schulte, D Vassilatis, E Stamboulis, E Dardiotis, I Patramani, Pm Kountra, C Vogiatzi, K Markou, P Tarantino, F Annesi, Anna Rita Bentivoglio, Arianna Guidubaldi, M Caccialupi, Francesca De Nigris, Nl Pedersen, J Reimer, J Lash, J Searcy, A. Strongosky

Risultato della ricerca: Contributo in rivista › Articolo in rivista › peer review

70 Citazioni (Scopus)

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.

Lingua originale	English
pagine (da-a)	778-792
Numero di pagine	15
Rivista	Annals of Neurology
DOI	https://doi.org/10.1002/ana.22321
Stato di pubblicazione	Pubblicato - 2011

Keywords

Parkinson disease
genetics

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10.1002/ana.22321

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Elbaz, A., Ross, O., Ioannidis, J., Soto Ortolaza, A., Aasly, J., Bozi, M., Chartier Harlin, M., Destée, A., Ferrarese, C., Ferraris, A., Gibson, J., Hadjigeorgiou, G., Jasinska Myga, B., Klein C, K. R., Lohmann, K., Loriot, M., Mellick, G., Mutez, E., Nilsson, C., ... Strongosky, A. (2011). Independent and joint effects of the MAPT and SNCA genes in Parkinson disease. Annals of Neurology, 778-792. https://doi.org/10.1002/ana.22321

@article{c0597761af9445d6841698ff8e56740e,

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 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.",

keywords = "Parkinson disease, genetics, Parkinson disease, genetics",

author = "A Elbaz and Oa Ross and Jp Ioannidis and {Soto Ortolaza}, Ai and J Aasly and M Bozi and {Chartier Harlin}, Mc and A Dest{\'e}e and C Ferrarese and A Ferraris and Jm Gibson and Gm Hadjigeorgiou and {Jasinska Myga}, B and {Klein C}, {Kr{\"u}ger R} and K Lohmann and Ma Loriot and Gd Mellick and E Mutez and C Nilsson and A Puschmann and A Quattrone and M Sharma and Pa Silburn and L Stefanis and Em Valente and {Vilari{\~n}o G{\"u}ell}, C and K Wirdefeldt and Zk Wszolek and G Xiromerisiou and Mj Farrer and P Amouyel and C Tzourio and C Mulot and Ja Bacon and Sa Cobb and Gt Sutherland and Ga Siebert and N Dissanayaka and Jd O'Sullivan and Rs Boyle and R Bordet and Jp Legendre and G Auburger and N Abahuni and S Winkler and T Gasser and O Riess and D Berg and C Schulte and D Vassilatis and E Stamboulis and E Dardiotis and I Patramani and Pm Kountra and C Vogiatzi and K Markou and P Tarantino and F Annesi and Bentivoglio, {Anna Rita} and Arianna Guidubaldi and M Caccialupi and {De Nigris}, Francesca and Nl Pedersen and J Reimer and J Lash and J Searcy and A. Strongosky",

year = "2011",

doi = "10.1002/ana.22321",

language = "English",

pages = "778--792",

journal = "Annals of Neurology",

issn = "0364-5134",

publisher = "John Wiley & Sons Inc.",

}

Elbaz, A, Ross, O, Ioannidis, J, Soto Ortolaza, A, Aasly, J, Bozi, M, Chartier Harlin, M, Destée, A, Ferrarese, C, Ferraris, A, Gibson, J, Hadjigeorgiou, G, Jasinska Myga, B, Klein C, KR, Lohmann, K, Loriot, M, Mellick, G, Mutez, E, Nilsson, C, Puschmann, A, Quattrone, A, Sharma, M, Silburn, P, Stefanis, L, Valente, E, Vilariño Güell, C, Wirdefeldt, K, Wszolek, Z, Xiromerisiou, G, Farrer, M, Amouyel, P, Tzourio, C, Mulot, C, Bacon, J, Cobb, S, Sutherland, G, Siebert, G, Dissanayaka, N, O'Sullivan, J, Boyle, R, Bordet, R, Legendre, J, Auburger, G, Abahuni, N, Winkler, S, Gasser, T, Riess, O, Berg, D, Schulte, C, Vassilatis, D, Stamboulis, E, Dardiotis, E, Patramani, I, Kountra, P, Vogiatzi, C, Markou, K, Tarantino, P, Annesi, F, Bentivoglio, AR, Guidubaldi, A, Caccialupi, M, De Nigris, F, Pedersen, N, Reimer, J, Lash, J, Searcy, J & Strongosky, A 2011, 'Independent and joint effects of the MAPT and SNCA genes in Parkinson disease', Annals of Neurology, pagg. 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, A

AU - Ross, Oa

AU - Ioannidis, Jp

AU - Soto Ortolaza, Ai

AU - Aasly, J

AU - Bozi, M

AU - Chartier Harlin, Mc

AU - Destée, A

AU - Ferrarese, C

AU - Ferraris, A

AU - Gibson, Jm

AU - Hadjigeorgiou, Gm

AU - Jasinska Myga, B

AU - Klein C, Krüger R

AU - Lohmann, K

AU - Loriot, Ma

AU - Mellick, Gd

AU - Mutez, E

AU - Nilsson, C

AU - Puschmann, A

AU - Quattrone, A

AU - Sharma, M

AU - Silburn, Pa

AU - Stefanis, L

AU - Valente, Em

AU - Vilariño Güell, C

AU - Wirdefeldt, K

AU - Wszolek, Zk

AU - Xiromerisiou, G

AU - Farrer, Mj

AU - Amouyel, P

AU - Tzourio, C

AU - Mulot, C

AU - Bacon, Ja

AU - Cobb, Sa

AU - Sutherland, Gt

AU - Siebert, Ga

AU - Dissanayaka, N

AU - O'Sullivan, Jd

AU - Boyle, Rs

AU - Bordet, R

AU - Legendre, Jp

AU - Auburger, G

AU - Abahuni, N

AU - Winkler, S

AU - Gasser, T

AU - Riess, O

AU - Berg, D

AU - Schulte, C

AU - Vassilatis, D

AU - Stamboulis, E

AU - Dardiotis, E

AU - Patramani, I

AU - Kountra, Pm

AU - Vogiatzi, C

AU - Markou, K

AU - Tarantino, P

AU - Annesi, F

AU - Bentivoglio, Anna Rita

AU - Guidubaldi, Arianna

AU - Caccialupi, M

AU - De Nigris, Francesca

AU - Pedersen, Nl

AU - Reimer, J

AU - Lash, J

AU - Searcy, J

AU - Strongosky, A.

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 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.

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 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.

KW - Parkinson disease

KW - genetics

KW - Parkinson disease

KW - genetics

UR - http://hdl.handle.net/10807/3133

U2 - 10.1002/ana.22321

DO - 10.1002/ana.22321

M3 - Article

SN - 0364-5134

SP - 778

EP - 792

JO - Annals of Neurology

JF - Annals of Neurology

ER -

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

Abstract

Keywords

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