Immunochip analysis identifies multiple susceptibility loci for systemic sclerosis

Mayes M.D., Bossini-Castillo L., Gorlova O., Martin J.E., Zhou X., Chen W.V., Assassi S., Ying J., Tan F.K., Arnett F.C., Reveille J.D., Guerra S., Teruel M., Carmona F.D., Gregersen P.K., Lee A.T., Lopez-Isac E., Ochoa E., Carreira P., Simeon C.P., Castellvi I., Gonzalez-Gay M.A., Zhernakova A., Padyukov L., Alarcon-Riquelme M., Wijmenga C., Brown M., Beretta L., Riemekasten G., Witte T., Hunzelmann N., Kreuter A., Distler J.H.W., Voskuyl A.E., Schuerwegh A.J., Hesselstrand R., Nordin A., Airo P., Lunardi C., Shiels P., Van Laar J.M., Herrick A., Worthington J., Denton C., Wigley F.M., Hummers L.K., Varga J., Hinchcliff M.E., Baron M., Hudson M., Pope J.E., Furst D.E., Khanna D., Phillips K., Schiopu E., Segal B.M., Molitor J.A., Silver R.M., Steen V.D., Simms R.W., Lafyatis R.A., Fessler B.J., Frech T.M., Alkassab F., Docherty P., Kaminska E., Khalidi N., Jones H.N., Markland J., Robinson D., Broen J., Radstake T.R.D.J., Fonseca C., Koeleman B.P. and Martin J. (2014) Immunochip analysis identifies multiple susceptibility loci for systemic sclerosis. American Journal of Human Genetics, 94 1: 47-61. doi:10.1016/j.ajhg.2013.12.002

Author Mayes M.D.
Bossini-Castillo L.
Gorlova O.
Martin J.E.
Zhou X.
Chen W.V.
Assassi S.
Ying J.
Tan F.K.
Arnett F.C.
Reveille J.D.
Guerra S.
Teruel M.
Carmona F.D.
Gregersen P.K.
Lee A.T.
Lopez-Isac E.
Ochoa E.
Carreira P.
Simeon C.P.
Castellvi I.
Gonzalez-Gay M.A.
Zhernakova A.
Padyukov L.
Alarcon-Riquelme M.
Wijmenga C.
Brown M.
Beretta L.
Riemekasten G.
Witte T.
Hunzelmann N.
Kreuter A.
Distler J.H.W.
Voskuyl A.E.
Schuerwegh A.J.
Hesselstrand R.
Nordin A.
Airo P.
Lunardi C.
Shiels P.
Van Laar J.M.
Herrick A.
Worthington J.
Denton C.
Wigley F.M.
Hummers L.K.
Varga J.
Hinchcliff M.E.
Baron M.
Hudson M.
Pope J.E.
Furst D.E.
Khanna D.
Phillips K.
Schiopu E.
Segal B.M.
Molitor J.A.
Silver R.M.
Steen V.D.
Simms R.W.
Lafyatis R.A.
Fessler B.J.
Frech T.M.
Alkassab F.
Docherty P.
Kaminska E.
Khalidi N.
Jones H.N.
Markland J.
Robinson D.
Broen J.
Radstake T.R.D.J.
Fonseca C.
Koeleman B.P.
Martin J.
Title Immunochip analysis identifies multiple susceptibility loci for systemic sclerosis
Journal name American Journal of Human Genetics   Check publisher's open access policy
ISSN 0002-9297
Publication date 2014-01
Year available 2014
Sub-type Article (original research)
DOI 10.1016/j.ajhg.2013.12.002
Open Access Status DOI
Volume 94
Issue 1
Start page 47
End page 61
Total pages 15
Place of publication Cambridge, United States
Publisher Cell Press
Collection year 2015
Language eng
Formatted 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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
UQ Diamantina Institute Publications
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