TY - JOUR
T1 - A genome-wide association study in multiple system atrophy
AU - On behalf of the European Multiple System Atrophy Study Group
AU - the UK Multiple System Atrophy Study Group
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
N1 - Publisher Copyright:
© 2016 American Academy of Neurology.
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 - https://www.scopus.com/pages/publications/84992046812
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 -