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 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. Mhyre & 27 others Huw 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, On behalf of the European Multiple System Atrophy Study Group, the UK Multiple System Atrophy Study Group

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 (US)
Pages (from-to)1591-1598
Number of pages8
JournalNeurology
Volume87
Issue number15
DOIs
StatePublished - Oct 11 2016
Externally publishedYes

Fingerprint

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

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Sailer, A., Scholz, S. W., Nalls, M. A., Schulte, C., Federoff, M., Price, T. R., ... the UK Multiple System Atrophy Study Group (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; 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; On behalf of the European Multiple System Atrophy Study Group; the UK Multiple System Atrophy Study Group.

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, A, 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, On behalf of the European Multiple System Atrophy Study Group & the UK Multiple System Atrophy Study Group 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 ; 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 ; On behalf of the European Multiple System Atrophy Study Group ; the UK Multiple System Atrophy Study Group. / A genome-wide association study in multiple system atrophy. In: Neurology. 2016 ; Vol. 87, No. 15. pp. 1591-1598.
@article{561aa266144e4456ab6c3ab109c3e91f,
title = "A genome-wide association study in multiple system atrophy",
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.",
author = "Anna Sailer and Scholz, {Sonja W.} and Nalls, {Michael A.} and Claudia Schulte and Monica Federoff and Price, {T. Ryan} and Andrew Lees and Ross, {Owen A.} and Dickson, {Dennis W.} and Kin Mok and Mencacci, {Niccolo E.} and Lucia Schottlaender and Viorica Chelban and Helen Ling and O'Sullivan, {Sean S.} and Wood, {Nicholas W.} and Traynor, {Bryan J.} and Luigi Ferrucci and Federoff, {Howard J.} and Mhyre, {Timothy R.} and Morris, {Huw R.} and G{\"u}nther Deuschl and Niall Quinn and Hakan Widner and Alberto Albanese and Jon Infante and Bhatia, {Kailash P.} and Werner Poewe and Wolfgang Oertel and H{\"o}glinger, {G{\"u}nter U.} and Ullrich W{\"u}llner and Stefano Goldwurm and Pellecchia, {Maria Teresa} and Joaquim Ferreira and Eduardo Tolosa and Bloem, {Bastiaan R.} and Olivier Rascol and Meissner, {Wassilios G.} and Hardy, {John A.} and Tamas Revesz and Holton, {Janice L.} and Thomas Gasser and Wenning, {Gregor K.} and Singleton, {Andrew B.} and Henry Houlden and {On behalf of the European Multiple System Atrophy Study Group} and {the UK Multiple System Atrophy Study Group}",
year = "2016",
month = "10",
day = "11",
doi = "10.1212/WNL.0000000000003221",
language = "English (US)",
volume = "87",
pages = "1591--1598",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "15",

}

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

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 - On behalf of the European Multiple System Atrophy Study Group

AU - the UK Multiple System Atrophy Study Group

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.

UR - http://www.scopus.com/inward/record.url?scp=84992046812&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84992046812&partnerID=8YFLogxK

U2 - 10.1212/WNL.0000000000003221

DO - 10.1212/WNL.0000000000003221

M3 - Article

VL - 87

SP - 1591

EP - 1598

JO - Neurology

JF - Neurology

SN - 0028-3878

IS - 15

ER -