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, 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
Neurology. 2016-09-14; 87(15): 1591-1598
DOI: 10.1212/WNL.0000000000003221


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1. Neurology. 2016 Oct 11;87(15):1591-1598. Epub 2016 Sep 14.

A genome-wide association study in multiple system atrophy.

Sailer A(1), Scholz SW(2), Nalls MA(1), Schulte C(1), Federoff M(1), Price TR(1),
Lees A(1), Ross OA(1), Dickson DW(1), Mok K(1), Mencacci NE(1), Schottlaender
L(1), Chelban V(1), Ling H(1), O’Sullivan SS(1), Wood NW(1), Traynor BJ(1),
Ferrucci L(1), Federoff HJ(1), Mhyre TR(1), Morris HR(1), Deuschl G(1), Quinn
N(1), Widner H(1), Albanese A(1), Infante J(1), Bhatia KP(1), Poewe W(1), Oertel
W(1), Höglinger GU(1), Wüllner U(1), Goldwurm S(1), Pellecchia MT(1), Ferreira
J(1), Tolosa E(1), Bloem BR(1), Rascol O(1), Meissner WG(1), Hardy JA(1), Revesz
T(1), Holton JL(1), Gasser T(1), Wenning GK(1), Singleton AB(1), Houlden H(2);
European Multiple System Atrophy Study Group and the UK Multiple System Atrophy
Study Group.

Author information:
(1)Authors’ affiliations are listed at the end of the article.
(2)Authors’ affiliations are listed at the end of the article.
.

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.

© 2016 American Academy of Neurology.

DOI: 10.1212/WNL.0000000000003221
PMCID: PMC5067544
PMID: 27629089 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus