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; Huw R. Morris; Günther Deuschl; Niall Quinn; Håkan 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

doi:10.1212/WNL.0000000000003221

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. MhyreHuw R. Morris, Günther Deuschl, Niall Quinn, Håkan 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

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

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 language	English
Pages (from-to)	1591-1598
Number of pages	8
Journal	Neurology
Volume	87
Issue number	15
DOIs	https://doi.org/10.1212/WNL.0000000000003221
Publication status	Published - 2016 Oct 11

Subject classification (UKÄ)

Neurology

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Sailer, A., Scholz, S. W., Nalls, M. A., Schulte, C., Federoff, M., Price, T. R., Lees, A., Ross, O. A., Dickson, D. W., Mok, K., Mencacci, N. E., Schottlaender, L., Chelban, V., Ling, H., O'Sullivan, S. S., Wood, N. W., Traynor, B. J., Ferrucci, L., Federoff, H. J., ... Houlden, H. (2016). A genome-wide association study in multiple system atrophy. Neurology, 87(15), 1591-1598. https://doi.org/10.1212/WNL.0000000000003221

@article{47e96b021a234f76aa25587d97c844b7,

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 H{\aa}kan 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",

year = "2016",

month = oct,

day = "11",

doi = "10.1212/WNL.0000000000003221",

language = "English",

volume = "87",

pages = "1591--1598",

journal = "Neurology",

issn = "0028-3878",

publisher = "Lippincott Williams & Wilkins",

number = "15",

}

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 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

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, Håkan

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

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

U2 - 10.1212/WNL.0000000000003221

DO - 10.1212/WNL.0000000000003221

M3 - Article

C2 - 27629089

AN - SCOPUS:84992046812

SN - 0028-3878

VL - 87

SP - 1591

EP - 1598

JO - Neurology

JF - Neurology

IS - 15

ER -

A genome-wide association study in multiple system atrophy

Abstract

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