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

Bossini-Castillo, Lara; Martin, Jose-Ezequiel; Broen, Jasper; Gorlova, Olga; Simeon, Carmen P.; Beretta, Lorenzo; Vonk, Madelon C.; Luis Callejas, Jose; Castellvi, Ivan and Carreira, Patricia, et al. (2012) In Human Molecular Genetics 21(4). p.926-933
Abstract
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... (More)
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. (Less)
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Human Molecular Genetics
volume
21
issue
4
pages
926 - 933
publisher
Oxford University Press
external identifiers
  • wos:000299792800017
  • scopus:84863043315
ISSN
0964-6906
DOI
10.1093/hmg/ddr522
language
English
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yes
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9b9aad4c-a364-4655-98e0-c49059781c6b (old id 2416098)
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2012-04-02 09:34:38
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2017-10-01 03:10:36
@article{9b9aad4c-a364-4655-98e0-c49059781c6b,
  abstract     = {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.},
  author       = {Bossini-Castillo, Lara and Martin, Jose-Ezequiel and Broen, Jasper and Gorlova, Olga and Simeon, Carmen P. and Beretta, Lorenzo and Vonk, Madelon C. and Luis Callejas, Jose and Castellvi, Ivan and Carreira, Patricia and Jose Garcia-Hernandez, Francisco and Fernandez Castro, Monica and Coenen, Marieke J. H. and Riemekasten, Gabriela and Witte, Torsten and Hunzelmann, Nicolas and Kreuter, Alexander and Distler, Joerg H. W. and Koeleman, Bobby P. and Voskuyl, Alexandre E. and Schuerwegh, Annemie J. and Palm, Oyvind and Hesselstrand, Roger and Nordin, Annika and Airo, Paolo and Lunardi, Claudio and Scorza, Raffaella and Shiels, Paul and van Laar, Jacob M. and Herrick, Ariane and Worthington, Jane and Denton, Christopher and Tan, Filemon K. and Arnett, Frank C. and Agarwal, Sandeep K. and Assassi, Shervin and Fonseca, Carmen and Mayes, Maureen D. and Radstake, Timothy R. D. J. and Martin, Javier},
  issn         = {0964-6906},
  language     = {eng},
  number       = {4},
  pages        = {926--933},
  publisher    = {Oxford University Press},
  series       = {Human Molecular Genetics},
  title        = {A GWAS follow-up study reveals the association of the IL12RB2 gene with systemic sclerosis in Caucasian populations},
  url          = {http://dx.doi.org/10.1093/hmg/ddr522},
  volume       = {21},
  year         = {2012},
}