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

Lookup NU author(s): Professor Jaap van Laar

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Abstract

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 x 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 x 10(-11), OR = 1.20) and JAZF1 (P = 1.11 x 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.


Publication metadata

Author(s): Martin JE, Assassi S, Diaz-Gallo LM, Broen JC, Simeon CP, Castellvi I, Vicente-Rabaneda E, Fonollosa V, Ortego-Centeno N, Gonzalez-Gay MA, Espinosa G, Carreira P, Camps M, Sabio JM, D'alfonso S, Vonk MC, Voskuyl AE, Schuerwegh AJ, Kreuter A, Witte T, Riemekasten G, Hunzelmann N, Airo P, Beretta L, Scorza R, Lunardi C, Van Laar J, Chee MM, Worthington J, Herrick A, Denton C, Fonseca C, Tan FK, Arnett F, Zhou XD, Reveille JD, Gorlova O, Koeleman BPC, Radstake TRDJ, Vyse T, Mayes MD, Alarcon-Riquelme ME, Martin J, Spanish Scleroderma Grp, SLEGEN Consortium, US Scleroderma GWAS Grp, BIOLUPUS

Publication type: Article

Publication status: Published

Journal: Human Molecular Genetics

Year: 2013

Volume: 22

Issue: 19

Pages: 4021-4029

Print publication date: 01/10/2013

Online publication date: 04/06/2013

Acceptance date: 28/05/2013

ISSN (print): 0964-6906

ISSN (electronic): 1460-2083

Publisher: Oxford University Press

URL: http://dx.doi.org/10.1093/hmg/ddt248

DOI: 10.1093/hmg/ddt248

PubMed id: 23740937


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Funding

Funder referenceFunder name
Fundacion Ramon Areces
Orphan Disease Program grant from the European League Against Rheumatism (EULAR)
Redes Tematicas de Investigacion Cooperativa Sanitaria Program
VIDI laureate from the Dutch Association of Research (NWO)
Dutch Arthritis Foundation (National Reumafonds)
ERC
European Science Foundation
Fondo Europeo de Desarrollo Regional (FEDER)
GEN-FER from the Spanish Society of Rheumatology
Swedish Research Council
1P50AR054144NIH/NIAMS Center of Research Translation in Scleroderma
1U01AI09090-01NIH NIAID
2008.40.001Dutch Diabetes Research Foundation
CTS-4977Junta de Andalucia (Spain)
K23-AR-061436
KFO 250
NR 09-1-408Dutch Arthritis Foundation (Reumafonds)
N01-AR-0-2251NIH/NIAMS Scleroderma Family Registry and DNA Repository
NIH/NIAMS-RO1-AR055258
PI0012Consejeria de Salud de Andalucia
PS09/00129Instituto de Salud Carlos III partially through FEDER funds of the European Union
RD08/0075Instituto de Salud Carlos III (ISCIII, Spain)
SAF2009-11110Ministerio de Economia y Competitividad
SAF2012-34435Ministerio de Economia y Competitividad
W81XWH-07-01-0111Department of Defense Congressionally Directed Medical Research Programs
WI 1031/6-1
TP03

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