| Literature DB >> 24387989 |
Maureen D Mayes1, Lara Bossini-Castillo2, Olga Gorlova3, José Ezequiel Martin4, Xiaodong Zhou5, Wei V Chen3, Shervin Assassi5, Jun Ying3, Filemon K Tan5, Frank C Arnett5, John D Reveille5, Sandra Guerra6, María Teruel4, Francisco David Carmona4, Peter K Gregersen7, Annette T Lee7, Elena López-Isac4, Eguzkine Ochoa4, Patricia Carreira8, Carmen Pilar Simeón9, Iván Castellví10, Miguel Ángel González-Gay11, Alexandra Zhernakova12, Leonid Padyukov13, Marta Alarcón-Riquelme14, Cisca Wijmenga12, Matthew Brown15, Lorenzo Beretta16, Gabriela Riemekasten17, Torsten Witte18, Nicolas Hunzelmann19, Alexander Kreuter20, Jörg H W Distler21, Alexandre E Voskuyl22, Annemie J Schuerwegh23, Roger Hesselstrand24, Annika Nordin13, Paolo Airó25, Claudio Lunardi26, Paul Shiels27, Jacob M van Laar28, Ariane Herrick29, Jane Worthington29, Christopher Denton6, Fredrick M Wigley30, Laura K Hummers30, John Varga31, Monique E Hinchcliff31, Murray Baron32, Marie Hudson32, Janet E Pope33, Daniel E Furst34, Dinesh Khanna35, Kristin Phillips35, Elena Schiopu35, Barbara M Segal36, Jerry A Molitor37, Richard M Silver38, Virginia D Steen39, Robert W Simms40, Robert A Lafyatis40, Barri J Fessler41, Tracy M Frech42, Firas Alkassab43, Peter Docherty44, Elzbieta Kaminska45, Nader Khalidi46, Henry Niall Jones47, Janet Markland48, David Robinson49, Jasper Broen50, Timothy R D J Radstake50, Carmen Fonseca6, Bobby P Koeleman51, Javier Martin4.
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.Entities:
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Year: 2014 PMID： 24387989 PMCID： PMC3882906 DOI： 10.1016/j.ajhg.2013.12.002
Source DB: PubMed Journal: Am J Hum Genet ISSN： 0002-9297 Impact factor: 11.025