A genome-wide association study in multiple system atrophy

Anna Sailer, Sonja W. Scholz, Michael A. Nalls, Claudia Schulte, Monica Federoff, T. Ryan Price, Andrew J. Lees, Owen A. Ross, Dennis W. Dickson, Kin Mok, Niccolo E. Mencacci, Lucia Schottlaender, Viorica Chelban, Helen Ling, Sean S. O'Sullivan, Nicholas W. Wood, Bryan J. Traynor, Luigi Ferrucci, Howard J. Federoff, Timothy R. MhyreHuw R. Morris, Günther Deuschl, Niall Quinn, Hakan Widner, Alberto Albanese, Jon Infante, Kailash P. Bhatia, Werner Poewe, Wolfgang Oertel, Günter U. Höglinger, Ullrich Wüllner, Stefano Goldwurm, Maria Teresa Pellecchia, Joaquim Ferreira, Eduardo Tolosa, Bastiaan R Bloem, Olivier Rascol, Wassilios G. Meissner, John A Hardy, Tamas Revesz, Janice L. Holton, Thomas Gasser, Gregor K. Wenning, Andrew B Singleton, Henry Houlden, European Multiple System Atrophy Study Group and the UK Multiple System Atrophy Study Group, Giovanna Calandra Buonaura, Sabina Capellari, Pietro Cortelli

Research output: Contribution to journalArticle

Abstract

OBJECTIVE: To identify genetic variants that play a role in the pathogenesis of multiple system atrophy (MSA), we undertook a genome-wide association study (GWAS).

METHODS: We performed a GWAS with >5 million genotyped and imputed single nucleotide polymorphisms (SNPs) in 918 patients with MSA of European ancestry and 3,864 controls. MSA cases were collected from North American and European centers, one third of which were neuropathologically confirmed.

RESULTS: We found no significant loci after stringent multiple testing correction. A number of regions emerged as potentially interesting for follow-up at p < 1 × 10(-6), including SNPs in the genes FBXO47, ELOVL7, EDN1, and MAPT. Contrary to previous reports, we found no association of the genes SNCA and COQ2 with MSA.

CONCLUSIONS: We present a GWAS in MSA. We have identified several potentially interesting gene loci, including the MAPT locus, whose significance will have to be evaluated in a larger sample set. Common genetic variation in SNCA and COQ2 does not seem to be associated with MSA. In the future, additional samples of well-characterized patients with MSA will need to be collected to perform a larger MSA GWAS, but this initial study forms the basis for these next steps.

Original languageEnglish
Pages (from-to)1591-1598
Number of pages8
JournalNeurology
Volume87
Issue number15
DOIs
Publication statusPublished - Oct 11 2016

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Multiple System Atrophy
Genome-Wide Association Study
Single Nucleotide Polymorphism
Genes

Keywords

  • Journal Article

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Sailer, A., Scholz, S. W., Nalls, M. A., Schulte, C., Federoff, M., Price, T. R., ... Cortelli, P. (2016). A genome-wide association study in multiple system atrophy. Neurology, 87(15), 1591-1598. https://doi.org/10.1212/WNL.0000000000003221

A genome-wide association study in multiple system atrophy. / Sailer, Anna; Scholz, Sonja W.; Nalls, Michael A.; Schulte, Claudia; Federoff, Monica; Price, T. Ryan; Lees, Andrew J.; Ross, Owen A.; Dickson, Dennis W.; Mok, Kin; Mencacci, Niccolo E.; Schottlaender, Lucia; Chelban, Viorica; Ling, Helen; O'Sullivan, Sean S.; Wood, Nicholas W.; Traynor, Bryan J.; Ferrucci, Luigi; Federoff, Howard J.; Mhyre, Timothy R.; Morris, Huw R.; Deuschl, Günther; Quinn, Niall; Widner, Hakan; Albanese, Alberto; Infante, Jon; Bhatia, Kailash P.; Poewe, Werner; Oertel, Wolfgang; Höglinger, Günter U.; Wüllner, Ullrich; Goldwurm, Stefano; Pellecchia, Maria Teresa; Ferreira, Joaquim; Tolosa, Eduardo; Bloem, Bastiaan R; Rascol, Olivier; Meissner, Wassilios G.; Hardy, John A; Revesz, Tamas; Holton, Janice L.; Gasser, Thomas; Wenning, Gregor K.; Singleton, Andrew B; Houlden, Henry; European Multiple System Atrophy Study Group and the UK Multiple System Atrophy Study Group ; Calandra Buonaura, Giovanna; Capellari, Sabina; Cortelli, Pietro.

In: Neurology, Vol. 87, No. 15, 11.10.2016, p. 1591-1598.

Research output: Contribution to journalArticle

Sailer, A, Scholz, SW, Nalls, MA, Schulte, C, Federoff, M, Price, TR, Lees, AJ, Ross, OA, Dickson, DW, Mok, K, Mencacci, NE, Schottlaender, L, Chelban, V, Ling, H, O'Sullivan, SS, Wood, NW, Traynor, BJ, Ferrucci, L, Federoff, HJ, Mhyre, TR, Morris, HR, Deuschl, G, Quinn, N, Widner, H, Albanese, A, Infante, J, Bhatia, KP, Poewe, W, Oertel, W, Höglinger, GU, Wüllner, U, Goldwurm, S, Pellecchia, MT, Ferreira, J, Tolosa, E, Bloem, BR, Rascol, O, Meissner, WG, Hardy, JA, Revesz, T, Holton, JL, Gasser, T, Wenning, GK, Singleton, AB, Houlden, H, European Multiple System Atrophy Study Group and the UK Multiple System Atrophy Study Group, Calandra Buonaura, G, Capellari, S & Cortelli, P 2016, 'A genome-wide association study in multiple system atrophy', Neurology, vol. 87, no. 15, pp. 1591-1598. https://doi.org/10.1212/WNL.0000000000003221
Sailer A, Scholz SW, Nalls MA, Schulte C, Federoff M, Price TR et al. A genome-wide association study in multiple system atrophy. Neurology. 2016 Oct 11;87(15):1591-1598. https://doi.org/10.1212/WNL.0000000000003221
Sailer, Anna ; Scholz, Sonja W. ; Nalls, Michael A. ; Schulte, Claudia ; Federoff, Monica ; Price, T. Ryan ; Lees, Andrew J. ; Ross, Owen A. ; Dickson, Dennis W. ; Mok, Kin ; Mencacci, Niccolo E. ; Schottlaender, Lucia ; Chelban, Viorica ; Ling, Helen ; O'Sullivan, Sean S. ; Wood, Nicholas W. ; Traynor, Bryan J. ; Ferrucci, Luigi ; Federoff, Howard J. ; Mhyre, Timothy R. ; Morris, Huw R. ; Deuschl, Günther ; Quinn, Niall ; Widner, Hakan ; Albanese, Alberto ; Infante, Jon ; Bhatia, Kailash P. ; Poewe, Werner ; Oertel, Wolfgang ; Höglinger, Günter U. ; Wüllner, Ullrich ; Goldwurm, Stefano ; Pellecchia, Maria Teresa ; Ferreira, Joaquim ; Tolosa, Eduardo ; Bloem, Bastiaan R ; Rascol, Olivier ; Meissner, Wassilios G. ; Hardy, John A ; Revesz, Tamas ; Holton, Janice L. ; Gasser, Thomas ; Wenning, Gregor K. ; Singleton, Andrew B ; Houlden, Henry ; European Multiple System Atrophy Study Group and the UK Multiple System Atrophy Study Group ; Calandra Buonaura, Giovanna ; Capellari, Sabina ; Cortelli, Pietro. / A genome-wide association study in multiple system atrophy. In: Neurology. 2016 ; Vol. 87, No. 15. pp. 1591-1598.
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TY - JOUR

T1 - A genome-wide association study in multiple system atrophy

AU - Sailer, Anna

AU - Scholz, Sonja W.

AU - Nalls, Michael A.

AU - Schulte, Claudia

AU - Federoff, Monica

AU - Price, T. Ryan

AU - Lees, Andrew J.

AU - Ross, Owen A.

AU - Dickson, Dennis W.

AU - Mok, Kin

AU - Mencacci, Niccolo E.

AU - Schottlaender, Lucia

AU - Chelban, Viorica

AU - Ling, Helen

AU - O'Sullivan, Sean S.

AU - Wood, Nicholas W.

AU - Traynor, Bryan J.

AU - Ferrucci, Luigi

AU - Federoff, Howard J.

AU - Mhyre, Timothy R.

AU - Morris, Huw R.

AU - Deuschl, Günther

AU - Quinn, Niall

AU - Widner, Hakan

AU - Albanese, Alberto

AU - Infante, Jon

AU - Bhatia, Kailash P.

AU - Poewe, Werner

AU - Oertel, Wolfgang

AU - Höglinger, Günter U.

AU - Wüllner, Ullrich

AU - Goldwurm, Stefano

AU - Pellecchia, Maria Teresa

AU - Ferreira, Joaquim

AU - Tolosa, Eduardo

AU - Bloem, Bastiaan R

AU - Rascol, Olivier

AU - Meissner, Wassilios G.

AU - Hardy, John A

AU - Revesz, Tamas

AU - Holton, Janice L.

AU - Gasser, Thomas

AU - Wenning, Gregor K.

AU - Singleton, Andrew B

AU - Houlden, Henry

AU - European Multiple System Atrophy Study Group and the UK Multiple System Atrophy Study Group

AU - Calandra Buonaura, Giovanna

AU - Capellari, Sabina

AU - Cortelli, Pietro

N1 - Ricercatori distaccati presso IRCCS a seguito Convenzione esclusiva con Università di Bologna (Calandra Buonaura Giovanna, Capellari Sabina, Cortelli Pietro)

PY - 2016/10/11

Y1 - 2016/10/11

N2 - OBJECTIVE: To identify genetic variants that play a role in the pathogenesis of multiple system atrophy (MSA), we undertook a genome-wide association study (GWAS).METHODS: We performed a GWAS with >5 million genotyped and imputed single nucleotide polymorphisms (SNPs) in 918 patients with MSA of European ancestry and 3,864 controls. MSA cases were collected from North American and European centers, one third of which were neuropathologically confirmed.RESULTS: We found no significant loci after stringent multiple testing correction. A number of regions emerged as potentially interesting for follow-up at p < 1 × 10(-6), including SNPs in the genes FBXO47, ELOVL7, EDN1, and MAPT. Contrary to previous reports, we found no association of the genes SNCA and COQ2 with MSA.CONCLUSIONS: We present a GWAS in MSA. We have identified several potentially interesting gene loci, including the MAPT locus, whose significance will have to be evaluated in a larger sample set. Common genetic variation in SNCA and COQ2 does not seem to be associated with MSA. In the future, additional samples of well-characterized patients with MSA will need to be collected to perform a larger MSA GWAS, but this initial study forms the basis for these next steps.

AB - OBJECTIVE: To identify genetic variants that play a role in the pathogenesis of multiple system atrophy (MSA), we undertook a genome-wide association study (GWAS).METHODS: We performed a GWAS with >5 million genotyped and imputed single nucleotide polymorphisms (SNPs) in 918 patients with MSA of European ancestry and 3,864 controls. MSA cases were collected from North American and European centers, one third of which were neuropathologically confirmed.RESULTS: We found no significant loci after stringent multiple testing correction. A number of regions emerged as potentially interesting for follow-up at p < 1 × 10(-6), including SNPs in the genes FBXO47, ELOVL7, EDN1, and MAPT. Contrary to previous reports, we found no association of the genes SNCA and COQ2 with MSA.CONCLUSIONS: We present a GWAS in MSA. We have identified several potentially interesting gene loci, including the MAPT locus, whose significance will have to be evaluated in a larger sample set. Common genetic variation in SNCA and COQ2 does not seem to be associated with MSA. In the future, additional samples of well-characterized patients with MSA will need to be collected to perform a larger MSA GWAS, but this initial study forms the basis for these next steps.

KW - Journal Article

U2 - 10.1212/WNL.0000000000003221

DO - 10.1212/WNL.0000000000003221

M3 - Article

C2 - 27629089

VL - 87

SP - 1591

EP - 1598

JO - Neurology

JF - Neurology

SN - 0028-3878

IS - 15

ER -