2024-03-28T14:46:05Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/618872022-03-28T10:18:59Zcom_10261_64com_10261_1col_10261_317
2012-12-04T11:43:45Z
urn:hdl:10261/61887
Identification of CSK as a systemic sclerosis genetic risk factor through genome wide association study follow-up
Martín, J. E.
Broen, Jasper C.
Carmona, F. David
Teruel, María
Simeón, Carmen P.
Vonk, Madelon C.
Slot, R. V.
Rodríguez-Rodríguez, Luis
Vicente, Esther
Fonollosa, V.
Ortego-Centeno, N.
González-Gay, M. A.
García-Hernández, Francisco José
García de la Peña, P.
Carreira, P.
Voskuyl, Alexandre E.
Schuerwegh, A. J.
Riel, Piet L.C.M. van
Kreuter, A.
Witte, Torsten
Riemekasten, G.
Airó, Paolo
Scorza, R.
Lunardi, C.
Hunzelmann, Nicolas
Distler, J. H.
Beretta, L.
Laar, Jacob M. van
Chee, M. M.
Worthington, J.
Herrick, A.
Denton, C.
Tan, F. K.
Arnett, F. C.
Assassi, S.
Fonseca, C.
Mayes, Maureen D.
Radstake, T. R.
Koeleman, B. P.
Martín, J.
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 5.04 3 10 -12, odds ratio (OR) 5 1.20]. Additionally, we found suggestive association in the loci PSD3 (P-value 5 3.18 3 10 -7, OR 5 1.36) and NFKB1 (P-value 5 1.03 3 10 -6, OR5 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. © The Author 2012. Published by Oxford University Press. All rights reserved.
2012-12-04T11:43:45Z
2012-12-04T11:43:45Z
2012
2012-12-04T11:43:45Z
artículo
Human Molecular Genetics 21: 2825- 2835 (2012)
http://hdl.handle.net/10261/61887
10.1093/hmg/dds099
22407130
eng
closedAccess
Oxford University Press