Identification of CSK as a systemic sclerosis genetic risk factor through Genome Wide Association Study follow-up.
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Publication year
2012Author(s)
Source
Human Molecular Genetics, 21, 12, (2012), pp. 2825-35ISSN
Publication type
Article / Letter to editor
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Organization
Rheumatology
Tumorimmunology
Journal title
Human Molecular Genetics
Volume
vol. 21
Issue
iss. 12
Page start
p. 2825
Page end
p. 35
Subject
NCEBP 2: Evaluation of complex medical interventions N4i 4: Auto-immunity, transplantation and immunotherapy; NCMLS 1: Infection and autoimmunity N4i 4: Auto-immunity, transplantation and immunotherapyAbstract
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 x 10(-12), odds ratio (OR) = 1.20]. Additionally, we found suggestive association in the loci PSD3 (P-value = 3.18 x 10(-7), OR = 1.36) and NFKB1 (P-value = 1.03 x 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.
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- Academic publications [245262]
- Electronic publications [132642]
- Faculty of Medical Sciences [93207]
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