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
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.
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U2 - 10.1093/hmg/ddt248
DO - 10.1093/hmg/ddt248
M3 - Article
C2 - 23740937
AN - SCOPUS:84888993757
VL - 22
SP - 4021
EP - 4029
JO - Human Molecular Genetics
JF - Human Molecular Genetics
SN - 0964-6906
IS - 19
ER -