Toggle Main Menu Toggle Search

Open Access padlockePrints

A GWAS follow-up study reveals the association of the IL12RB2 gene with systemic sclerosis in Caucasian populations

Lookup NU author(s): Professor Jaap Van Laar


Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


A single-nucleotide polymorphism (SNP) at the IL12RB2 locus showed a suggestive association signal in a previously published genome-wide association study (GWAS) in systemic sclerosis (SSc). Aiming to reveal the possible implication of the IL12RB2 gene in SSc, we conducted a follow-up study of this locus in different Caucasian cohorts. We analyzed 10 GWAS-genotyped SNPs in the IL12RB2 region (2309 SSc patients and 5161 controls). We then selected three SNPs (rs3790567, rs3790566 and rs924080) based on their significance level in the GWAS, for follow-up in an independent European cohort comprising 3344 SSc and 3848 controls. The most-associated SNP (rs3790567) was further tested in an independent cohort comprising 597 SSc patients and 1139 controls from the USA. After conditional logistic regression analysis of the GWAS data, we selected rs3790567 [P-MH = 1.92 x 10(-5) odds ratio (OR) = 1.19] as the genetic variant with the firmest independent association observed in the analyzed GWAS peak of association. After the first follow-up phase, only the association of rs3790567 was consistent (P-MH = 4.84 x 10(-3) OR = 1.12). The second follow-up phase confirmed this finding (P-chi 2 = 2.82 x 10(-4) OR = 1.34). After performing overall pooled-analysis of all the cohorts included in the present study, the association found for the rs3790567 SNP in the IL12RB2 gene region reached GWAS-level significant association (P-MH = 2.82 x 10(-9) OR = 1.17). Our data clearly support the IL12RB2 genetic association with SSc, and suggest a relevant role of the interleukin 12 signaling pathway in SSc pathogenesis.

Publication metadata

Author(s): Bossini-Castillo L, Martin JE, Broen J, Gorlova O, Simeon CP, Beretta L, Vonk MC, Callejas JL, Castellvi I, Carreira P, Garcia-Hernandez FJ, Castro MF, Coenen MJH, Riemekasten G, Witte T, Hunzelmann N, Kreuter A, Distler JHW, Koeleman BP, Voskuyl AE, Schuerwegh AJ, Palm O, Hesselstrand R, Nordin A, Airo P, Lunardi C, Scorza R, Shiels P, van Laar JM, Herrick A, Worthington J, Denton C, Tan FK, Arnett FC, Agarwal SK, Assassi S, Fonseca C, Mayes MD, Radstake TRDJ, Martin J, Spanish Scleroderma Grp

Publication type: Article

Publication status: Published

Journal: Human Molecular Genetics

Year: 2012

Volume: 21

Issue: 4

Pages: 926-933

Print publication date: 10/11/2011

ISSN (print): 0964-6906

ISSN (electronic): 1460-2083

Publisher: Oxford University Press


DOI: 10.1093/hmg/ddr522


Altmetrics provided by Altmetric


Funder referenceFunder name
VIDI laureate from the Dutch Association of Research (NWO)
Dutch Arthritis Foundation (National Reumafonds)
European League Against Rheumatism (EULAR)
Fondo Europeo de Desarrollo Regional (FEDER)
GEN-FER from the Spanish Society of Rheumatology
Redes Tematicas de Investigacion Cooperativa Sanitaria
1P50AR054144NIH/NIAMS Center of Research Translation in Scleroderma
2008.40.001Dutch Diabetes Research Foundation
1031/6.1DFG WI
CTS-4977Junta de Andalucia, Spain
N01-AR-0-2251NIH/NIAMS Scleroderma Registry and DNA Repository
PI-0590-2010Consejeria de Salud, Junta de Andalucia, Spain
NR09-1-408Dutch Arthritis Foundation (Reumafonds)
RD08/0075(RIER) from Instituto de Salud Carlos III (ISCIII), Spain
W81XWH-07-01-0111Department of Defense
SAF2009-11110Spanish Ministry of Science