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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. and Mok, Kin, et al. (2016) In Neurology 87(15). p.1591-1598
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... (More)

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.

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Neurology
volume
87
issue
15
pages
8 pages
publisher
American Academy of Neurology
external identifiers
  • scopus:84992046812
  • wos:000392228600017
ISSN
0028-3878
DOI
10.1212/WNL.0000000000003221
language
English
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yes
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47e96b02-1a23-4f76-aa25-587d97c844b7
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2016-11-08 16:20:44
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2017-11-19 04:34:40
@article{47e96b02-1a23-4f76-aa25-587d97c844b7,
  abstract     = {<p>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 &gt;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 &lt; 1 × 10<sup>-6</sup>, 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.</p>},
  author       = {Sailer, Anna and Scholz, Sonja W. and Nalls, Michael A. and Schulte, Claudia and Federoff, Monica and Price, T. Ryan and Lees, Andrew and Ross, Owen A. and Dickson, Dennis W. and Mok, Kin and Mencacci, Niccolo E. and Schottlaender, Lucia and Chelban, Viorica and Ling, Helen and O'Sullivan, Sean S. and Wood, Nicholas W. and Traynor, Bryan J. and Ferrucci, Luigi and Federoff, Howard J. and Mhyre, Timothy R. and Morris, Huw R. and Deuschl, Günther and Quinn, Niall and Widner, Håkan and Albanese, Alberto and Infante, Jon and Bhatia, Kailash P. and Poewe, Werner and Oertel, Wolfgang and Höglinger, Günter U. and Wüllner, Ullrich and Goldwurm, Stefano and Pellecchia, Maria Teresa and Ferreira, Joaquim and Tolosa, Eduardo and Bloem, Bastiaan R. and Rascol, Olivier and Meissner, Wassilios G. and Hardy, John A. and Revesz, Tamas and Holton, Janice L. and Gasser, Thomas and Wenning, Gregor K. and Singleton, Andrew B. and Houlden, Henry},
  issn         = {0028-3878},
  language     = {eng},
  month        = {10},
  number       = {15},
  pages        = {1591--1598},
  publisher    = {American Academy of Neurology},
  series       = {Neurology},
  title        = {A genome-wide association study in multiple system atrophy},
  url          = {http://dx.doi.org/10.1212/WNL.0000000000003221},
  volume       = {87},
  year         = {2016},
}