TY - JOUR
T1 - A GWAS follow-up study reveals the association of the IL12RB2 gene with systemic sclerosis in Caucasian populations
AU - Bossini-Castillo, Lara
AU - Martin, Jose Ezequiel
AU - Broen, Jasper
AU - Gorlova, Olga
AU - Simeón, Carmen P.
AU - Beretta, Lorenzo
AU - Vonk, Madelon C.
AU - Callejas, Jose Luis
AU - Castellví, Ivan
AU - Carreira, Patricia
AU - García-Hernández, Francisco José
AU - Castro, Mónica Fernández
AU - Coenen, Marieke J.H.
AU - Riemekasten, Gabriela
AU - Witte, Torsten
AU - Hunzelmann, Nicolas
AU - Kreuter, Alexander
AU - Distler, Jörg H.W.
AU - Koeleman, Bobby P.
AU - Voskuyl, Alexandre E.
AU - Schuerwegh, Annemie J.
AU - Palm, Øyvind
AU - Hesselstrand, Roger
AU - Nordin, Annika
AU - Airó, Paolo
AU - Lunardi, Claudio
AU - Scorza, Raffaella
AU - Shiels, Paul
AU - van Laar, Jacob M.
AU - Herrick, Ariane
AU - Worthington, Jane
AU - Denton, Christopher
AU - Tan, Filemon K.
AU - Arnett, Frank C.
AU - Agarwal, Sandeep K.
AU - Assassi, Shervin
AU - Fonseca, Carmen
AU - Mayes, Maureen D.
AU - Radstake, Timothy R.D.J.
AU - Martin, Javier
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2012/2
Y1 - 2012/2
N2 - 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 [PMH5 1.92 3 10 -5 odds ratio (OR) 5 1.19] as the genetic variant with the firmest independent association observed in the analyzedGWASpeak of association. After the first follow-up phase, only the association of rs3790567 was consistent (PMH5 4.84 3 10 -3OR 5 1.12). The second follow-up phase confirmed this finding (Px2 5 2.82 3 10 -4 OR 5 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 (PMH5 2.82 3 10 -9 OR 5 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.
AB - 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 [PMH5 1.92 3 10 -5 odds ratio (OR) 5 1.19] as the genetic variant with the firmest independent association observed in the analyzedGWASpeak of association. After the first follow-up phase, only the association of rs3790567 was consistent (PMH5 4.84 3 10 -3OR 5 1.12). The second follow-up phase confirmed this finding (Px2 5 2.82 3 10 -4 OR 5 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 (PMH5 2.82 3 10 -9 OR 5 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.
UR - http://www.scopus.com/inward/record.url?scp=84863043315&partnerID=8YFLogxK
U2 - 10.1093/hmg/ddr522
DO - 10.1093/hmg/ddr522
M3 - Journal articles
C2 - 22076442
AN - SCOPUS:84863043315
SN - 0964-6906
VL - 21
SP - 926
EP - 933
JO - Human Molecular Genetics
JF - Human Molecular Genetics
IS - 4
M1 - ddr522
ER -