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Enrichment of associations in genes with fibrosis, apoptosis, and innate immunity functions with cardiac manifestation of neonatal lupus
Arthritis & Rheumatism, 08/09/2012
Ramos PS et al. – This study identified novel candidate genes associated with cardiac–neonatal lupus and highlights the value of this cohort in advancing the knowledge regarding the genetic etiology of this syndrome. Identification of causal alleles is expected to provide critical insight into the molecular mechanisms responsible for linking maternal autoantibodies to cardiac scarring in these fetuses/neonates.
Methods- Using data from the genome-wide association study (GWAS) in 116 cardiac-NL Caucasian children and 3,351 Caucasian controls, the authors tested for enrichment of SNP associations in genes with candidate biological functions related to fibrosis, immune, apoptosis, T cell function, cell infiltration, innate immune cell function, interferon, Toll like receptors and calcium channels.
- After linkage disequilibrium pruning and exclusion of the extended HLA region, a total of 15,103 SNPs in 3,068 genes remained.
- A highly significant enrichment of P-values was observed in genes related to fibrosis (P=2.27×10-9), apoptosis (P=7.67×10-7), innate immune cell (P=2.53×10-6), immune (P=5.01×10-4), T cell (P=2.23×10-4), and interferon functions (P=1.64×10-3).
- The most significant non-HLA associations included the sialyltransferase ST8SIA2 (rs1487982, P=3.38×10-5, OR [95%CI]=2.20 [1.52-3.19]), the integrin ITGA1 (rs2432143, P=4.54×10-5, OR [95%CI]=2.31 [1.54-3.45]), and the complement regulator CSMD1 (rs7002001, P=6.33×10-5, OR [95%CI]=2.41 [1.57-3.72]).
