A systemic sclerosis and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci

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...

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Bibliographic Details
Main Authors: Martin Jose-Ezequiel
Assassi Shervin
Diaz-Gallo Lina-Marcela
Broen Jasper C
Simeon Carmen P
Castellvi Ivan
Vicente-Rabaneda Esther
Fonollosa Vicente
Ortego-Centeno Norberto
González-Gay Miguel A
Espinosa Gerard
Carreira Patricia
Kollaborációs szervezet: Spanish Scleroderma Group
Kollaborációs szervezet: SLEGEN consortium
Kollaborációs szervezet: U.S. Scleroderma GWAS group
Kollaborációs szervezet: BIOLUPUS
Camps Mayte
Sabio Jose M
D'alfonso Sandra
Vonk Madelon C
Voskuyl Alexandre E
Schuerwegh Annemie J
Kreuter Alexander
Witte Torsten
Riemekasten Gabriella
Hunzelmann Nicolas
Airo Paolo
Beretta Lorenzo
Scorza Raffaella
Lunardi Claudio
Endreffy Emőke
Kovács László
Format: Article
Published: 2013
Series:HUMAN MOLECULAR GENETICS 22 No. 19
Subjects:
doi:10.1093/hmg/ddt248

mtmt:31136274
Online Access:http://publicatio.bibl.u-szeged.hu/29520
Description
Summary: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.
Physical Description:4021-4029
ISSN:0964-6906