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Immunochip analysis identifies multiple susceptibility Loci for systemic sclerosis.

Mayes, Maureen D; Bossini-Castillo, Lara; Gorlova, Olga; Martin, José Ezequiel; Zhou, Xiaodong; Chen, Wei V; Assassi, Shervin; Ying, Jun; Tan, Filemon K and Arnett, Frank C, et al. (2014) In American Journal of Human Genetics 94(1). p.47-61
Abstract
In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic amino acid positions and seven SNPs that explained the observed significant associations in the region. In addition, a replication step comprising 4,017 SSc cases and 5,935 controls was carried out for several selected non-HLA variants, reaching a total of 5,850 cases and 9,401 controls of European ancestry. Following this strategy, we identified and validated three SSc risk loci, including DNASE1L3 at 3p14, the SCHIP1-IL12A locus at 3q25, and... (More)
In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic amino acid positions and seven SNPs that explained the observed significant associations in the region. In addition, a replication step comprising 4,017 SSc cases and 5,935 controls was carried out for several selected non-HLA variants, reaching a total of 5,850 cases and 9,401 controls of European ancestry. Following this strategy, we identified and validated three SSc risk loci, including DNASE1L3 at 3p14, the SCHIP1-IL12A locus at 3q25, and ATG5 at 6q21, as well as a suggested association of the TREH-DDX6 locus at 11q23. The associations of several previously reported SSc risk loci were validated and further refined, and the observed peak of association in PXK was related to DNASE1L3. Our study has increased the number of known genetic associations with SSc, provided further insight into the pleiotropic effects of shared autoimmune risk factors, and highlighted the power of dense mapping for detecting previously overlooked susceptibility loci. (Less)
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American Journal of Human Genetics
volume
94
issue
1
pages
47 - 61
publisher
Cell Press
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  • wos:000329888400005
  • pmid:24387989
  • scopus:84891817885
ISSN
0002-9297
DOI
10.1016/j.ajhg.2013.12.002
language
English
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yes
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66896325-ff51-4492-bbad-7c5d785acae9 (old id 4292055)
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http://www.ncbi.nlm.nih.gov/pubmed/24387989?dopt=Abstract
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2014-02-06 21:23:36
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@article{66896325-ff51-4492-bbad-7c5d785acae9,
  abstract     = {In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic amino acid positions and seven SNPs that explained the observed significant associations in the region. In addition, a replication step comprising 4,017 SSc cases and 5,935 controls was carried out for several selected non-HLA variants, reaching a total of 5,850 cases and 9,401 controls of European ancestry. Following this strategy, we identified and validated three SSc risk loci, including DNASE1L3 at 3p14, the SCHIP1-IL12A locus at 3q25, and ATG5 at 6q21, as well as a suggested association of the TREH-DDX6 locus at 11q23. The associations of several previously reported SSc risk loci were validated and further refined, and the observed peak of association in PXK was related to DNASE1L3. Our study has increased the number of known genetic associations with SSc, provided further insight into the pleiotropic effects of shared autoimmune risk factors, and highlighted the power of dense mapping for detecting previously overlooked susceptibility loci.},
  author       = {Mayes, Maureen D and Bossini-Castillo, Lara and Gorlova, Olga and Martin, José Ezequiel and Zhou, Xiaodong and Chen, Wei V and Assassi, Shervin and Ying, Jun and Tan, Filemon K and Arnett, Frank C and Reveille, John D and Guerra, Sandra and Teruel, María and Carmona, Francisco David and Gregersen, Peter K and Lee, Annette T and López-Isac, Elena and Ochoa, Eguzkine and Carreira, Patricia and Simeón, Carmen Pilar and Castellví, Iván and González-Gay, Miguel Ángel and Zhernakova, Alexandra and Padyukov, Leonid and Alarcón-Riquelme, Marta and Wijmenga, Cisca and Brown, Matthew and Beretta, Lorenzo and Riemekasten, Gabriela and Witte, Torsten and Hunzelmann, Nicolas and Kreuter, Alexander and Distler, Jörg H W and Voskuyl, Alexandre E and Schuerwegh, Annemie J and Hesselstrand, Roger and Nordin, Annika and Airó, Paolo and Lunardi, Claudio and Shiels, Paul and van Laar, Jacob M and Herrick, Ariane and Worthington, Jane and Denton, Christopher and Wigley, Fredrick M and Hummers, Laura K and Varga, John and Hinchcliff, Monique E and Baron, Murray and Hudson, Marie and Pope, Janet E and Furst, Daniel E and Khanna, Dinesh and Phillips, Kristin and Schiopu, Elena and Segal, Barbara M and Molitor, Jerry A and Silver, Richard M and Steen, Virginia D and Simms, Robert W and Lafyatis, Robert A and Fessler, Barri J and Frech, Tracy M and Alkassab, Firas and Docherty, Peter and Kaminska, Elzbieta and Khalidi, Nader and Jones, Henry Niall and Markland, Janet and Robinson, David and Broen, Jasper and Radstake, Timothy R D J and Fonseca, Carmen and Koeleman, Bobby P and Martin, Javier},
  issn         = {0002-9297},
  language     = {eng},
  number       = {1},
  pages        = {47--61},
  publisher    = {Cell Press},
  series       = {American Journal of Human Genetics},
  title        = {Immunochip analysis identifies multiple susceptibility Loci for systemic sclerosis.},
  url          = {http://dx.doi.org/10.1016/j.ajhg.2013.12.002},
  volume       = {94},
  year         = {2014},
}