AI Article Synopsis
- Systemic sclerosis (SSc) is a complex autoimmune disease influenced by genetics and environment, with a new study focusing on its genetic components through a genome-wide association study (GWAS).
- A large replication study involving 768 selected polymorphisms was conducted across seven cohorts in Europe, including a total of over 9,000 individuals for better validation of genetic links to SSc.
- The research identified a novel genetic risk locus (CSK) and suggested associations with PSD3 and NFKB1, while also reinforcing the link to previously recognized genetic factors related to the disease.
Article Abstract
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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3368627 | PMC |
| http://dx.doi.org/10.1093/hmg/dds099 | DOI Listing |
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