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Lookup NU author(s): Professor Jaap Van Laar
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Systemic sclerosis (SSc) is complex autoimmune disease affecting the connective tissue; influenced by genetic and environmental components. Recently, we performed the first successful genome-wide association study (GWAS) of SSc. Here, we perform a large replication study to better dissect the genetic component of SSc. We selected 768 polymorphisms from the previous GWAS and genotyped them in seven replication cohorts from Europe. Overall significance was calculated for replicated significant SNPs by meta-analysis of the replication cohorts and replication-GWAS cohorts (3237 cases and 6097 controls). Six SNPs in regions not previously associated with SSc were selected for validation in another five independent cohorts, up to a total of 5270 SSc patients and 8326 controls. We found evidence for replication and overall genome-wide significance for one novel SSc genetic risk locus: CSK [P-value 5.04 10(12), odds ratio (OR) 1.20]. Additionally, we found suggestive association in the loci PSD3 (P-value 3.18 10(7), OR 1.36) and NFKB1 (P-value 1.03 10(6), OR 1.14). Additionally, we strengthened the evidence for previously confirmed associations. This study significantly increases the number of known putative genetic risk factors for SSc, including the genes CSK, PSD3 and NFKB1, and further confirms six previously described ones.
Author(s): Martin JE, Broen JC, Carmona FD, Teruel M, Simeon CP, Vonk MC, van 't Slot R, Rodriguez-Rodriguez L, Vicente E, Fonollosa V, Ortego-Centeno N, Gonzalez-Gay MA, Garcia-Hernandez FJ, de la Pena PG, Carreira P, Voskuyl AE, Schuerwegh AJ, van Riel PLCM, Kreuter A, Witte T, Riemekasten G, Airo P, Scorza R, Lunardi C, Hunzelmann N, Distler JHW, Beretta L, van Laar J, Chee MM, Worthington J, Herrick A, Denton C, Tan FK, Arnett FC, Assassi S, Fonseca C, Mayes MD, Radstake TRDJ, Koeleman BPC, Martin J, Spanish Schleroderma Grp
Publication type: Article
Publication status: Published
Journal: Human Molecular Genetics
Year: 2012
Volume: 21
Issue: 12
Pages: 2825-2835
Print publication date: 09/03/2012
ISSN (print): 0964-6906
ISSN (electronic): 1460-2083
Publisher: Oxford University Press
URL: http://dx.doi.org/10.1093/hmg/dds099
DOI: 10.1093/hmg/dds099
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