TY - JOUR
T1 - A systemic sclerosis and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci
AU - Martin, Jose Ezequiel
AU - Assassi, Shervin
AU - Diaz-Gallo, Lina Marcela
AU - Broen, Jasper C.
AU - Simeon, Carmen P.
AU - Castellvi, Ivan
AU - Vicente-Rabaneda, Esther
AU - Fonollosa, Vicente
AU - Ortego-Centeno, Norberto
AU - González-Gay, Miguel A.
AU - Espinosa, Gerard
AU - Carreira, Patricia
AU - Camps, Mayte
AU - Sabio, Jose M.
AU - D'alfonso, Sandra
AU - Vonk, Madelon C.
AU - Voskuyl, Alexandre E.
AU - Schuerwegh, Annemie J.
AU - Kreuter, Alexander
AU - Witte, Torsten
AU - Riemekasten, Gabriella
AU - Hunzelmann, Nicolas
AU - Airo, Paolo
AU - Beretta, Lorenzo
AU - Scorza, Raffaella
AU - Lunardi, Claudio
AU - Van Laar, Jacob
AU - Chee, Meng May
AU - Worthington, Jane
AU - Herrick, Arianne
AU - Denton, Christopher
AU - Fonseca, Carmen
AU - Tan, Filemon K.
AU - Arnett, Frank
AU - Zhou, Xiaodong
AU - Reveille, John D.
AU - Gorlova, Olga
AU - Koeleman, Bobby P.C.
AU - Radstake, Timothy R.D.J.
AU - Vyse, Timothy
AU - Mayes, Maureen D.
AU - Alarcón-Riquelme, Marta E.
AU - Martin, Javier
N1 - Funding Information:
This work was supported by the following grants: J.M. was funded by GEN-FER from the Spanish Society of Rheumatology, SAF2009-11110 and SAF2012-34435 from the Ministerio de Economia y Competitividad, CTS-4977 from Junta de Andalucía (Spain), Redes Temáticas de Investigación Coopera-tiva Sanitaria Program, RD08/0075 (RIER) from Instituto de Salud Carlos III (ISCIII, Spain), Fondo Europeo de Desarrollo Regional (FEDER) and the grant NIH NIAID 1U01AI09090-01. T.R.D.J.R. was funded by the VIDI laureate from the Dutch Association of Research (NWO) and Dutch Arthritis Foundation (National Reumafonds) and is an ERC starting grant Laureate 2011. J.M. and T.R.D.J.R. were sponsored by the Orphan Disease Program grant from the European League Against Rheumatism (EULAR). B.P.C.K. is supported by the Dutch Diabetes Research Foundation (grant 2008.40.001) and the Dutch Arthritis Foundation (Reumafonds, grant NR 09-1-408). S.A. and M.D.M. were supported by NIH/NIAMS Scleroderma Family Registry and DNA Repository (N01-AR-0-2251), NIH/NIAMS-RO1-AR055258, and NIH/ NIAMS Center of Research Translation in Scleroderma (1P50AR054144), the Department of Defense Congressionally Directed Medical Research Programs (W81XWH-07-01-0111), and K23-AR-061436. M.E.A.R. was funded by the Instituto de Salud Carlos III partially through FEDER funds of the European Union (PS09/00129), la Consejería de Salud de Andalucía (PI0012), la Fundación Ramón Areces and the Swedish Research Council. M.E.A.R. is the Chairman of the BIOLUPUS network funded by the European Science Foundation. T.W. is funded by the grant KFO 250, TP03, WI 1031/6-1.
PY - 2013/10
Y1 - 2013/10
N2 - Systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) are two archetypal systemic autoimmune diseases which have been shown to share multiple genetic susceptibility loci. In order to gain insight into the genetic basis of these diseases, we performed a pan-meta-analysis of two genome-wide association studies (GWASs) together with a replication stage including additional SSc and SLE cohorts. This increased the sample size to a total of 21 109 (6835 cases and 14 274 controls). We selected for replication 19 SNPs from the GWAS data. We were able to validate KIAA0319L (P = 3.31 × 10-11, OR = 1.49) as novel susceptibility loci for SSc and SLE. Furthermore, we also determined that the previously described SLE susceptibility loci PXK (P = 3.27 × 10-11, OR = 1.20) and JAZF1 (P = 1.11 × 10-8, OR = 1.13) are shared with SSc. Supporting these new discoveries, we observed that KIAA0319L was overexpressed in peripheral blood cells of SSc and SLE patients compared with healthy controls. With these, we add three (KIAA0319L, PXK and JAZF1) and one (KIAA0319L) new susceptibility loci for SSc and SLE, respectively, increasing significantly the knowledge of the genetic basis of autoimmunity.
AB - Systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) are two archetypal systemic autoimmune diseases which have been shown to share multiple genetic susceptibility loci. In order to gain insight into the genetic basis of these diseases, we performed a pan-meta-analysis of two genome-wide association studies (GWASs) together with a replication stage including additional SSc and SLE cohorts. This increased the sample size to a total of 21 109 (6835 cases and 14 274 controls). We selected for replication 19 SNPs from the GWAS data. We were able to validate KIAA0319L (P = 3.31 × 10-11, OR = 1.49) as novel susceptibility loci for SSc and SLE. Furthermore, we also determined that the previously described SLE susceptibility loci PXK (P = 3.27 × 10-11, OR = 1.20) and JAZF1 (P = 1.11 × 10-8, OR = 1.13) are shared with SSc. Supporting these new discoveries, we observed that KIAA0319L was overexpressed in peripheral blood cells of SSc and SLE patients compared with healthy controls. With these, we add three (KIAA0319L, PXK and JAZF1) and one (KIAA0319L) new susceptibility loci for SSc and SLE, respectively, increasing significantly the knowledge of the genetic basis of autoimmunity.
UR - http://www.scopus.com/inward/record.url?scp=84888993757&partnerID=8YFLogxK
U2 - 10.1093/hmg/ddt248
DO - 10.1093/hmg/ddt248
M3 - Article
SN - 0964-6906
VL - 22
SP - 4021
EP - 4029
JO - Human Molecular Genetics
JF - Human Molecular Genetics
IS - 19
ER -