Immunochip analysis identifies multiple susceptibility loci for systemic sclerosis Mayes, Maureen D. Bossini Castillo, Lara María Alarcón Riquelme, Marta Eugenia Martín Ibáñez, Javier Existe versión de acceso abierto proporcionado por la revista 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. 2024-02-07T10:12:36Z 2024-02-07T10:12:36Z 2014 info:eu-repo/semantics/article Mayes MD, Bossini-Castillo L, Gorlova O, Martin JE, Zhou X, Chen WV, Assassi S, Ying J, Tan FK, Arnett FC, Reveille JD, Guerra S, Teruel M, Carmona FD, Gregersen PK, Lee AT, López-Isac E, Ochoa E, Carreira P, Simeón CP, Castellví I, González-Gay MÁ; Spanish Scleroderma Group; Zhernakova A, Padyukov L, Alarcón-Riquelme M, Wijmenga C, Brown M, Beretta L, Riemekasten G, Witte T, Hunzelmann N, Kreuter A, Distler JH, Voskuyl AE, Schuerwegh AJ, Hesselstrand R, Nordin A, Airó P, Lunardi C, Shiels P, van Laar JM, Herrick A, Worthington J, Denton C, Wigley FM, Hummers LK, Varga J, Hinchcliff ME, Baron M, Hudson M, Pope JE, Furst DE, Khanna D, Phillips K, Schiopu E, Segal BM, Molitor JA, Silver RM, Steen VD, Simms RW, Lafyatis RA, Fessler BJ, Frech TM, Alkassab F, Docherty P, Kaminska E, Khalidi N, Jones HN, Markland J, Robinson D, Broen J, Radstake TR, Fonseca C, Koeleman BP, Martin J. Immunochip analysis identifies multiple susceptibility loci for systemic sclerosis. Am J Hum Genet. 2014 Jan 2;94(1):47-61. doi: 10.1016/j.ajhg.2013.12.002. PMID: 24387989; PMCID: PMC3882906. https://hdl.handle.net/10481/88530 10.1016/j.ajhg.2013.12.002 eng info:eu-repo/semantics/openAccess Elsevier