Systematic Confirmation Study of GWAS-Identified Genetic Variants for Kawasaki Disease in A Chinese Population

Abstract

Genome-wide association studies (GWASs) have identified multiple single nucleotide polymorphisms (SNPs) associated with Kawasaki disease (KD). In this study, we replicated the associations of 10 GWAS-identified SNPs with KD in a Han Chinese population. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression, and cumulative effect of non-risk genotypes were also performed. Although none of the SNPs reached the corrected significance level, 4 SNPs showed nominal associations with KD risk. Compared with their respective wild type counterparts, rs1801274 AG+GG genotypes and rs3818298 TC+CC genotypes were nominally associated with the reduced risk of KD (OR = 0.77, 95% CI = 0.59–0.99, P = 0.045; OR = 0.74, 95% CI = 0.56–0.98, P = 0.038). Meanwhile, rs1801274 GG genotype, rs2736340 CC genotype or rs4813003 TT genotype showed a reduced risk trend (OR = 0.57, 95% CI = 0.35–0.93, P = 0.024; OR = 0.46, 95% CI = 0.26–0.83, P = 0.010; OR = 0.64, 95% CI = 0.43–0.94, P = 0.022), compared with rs1801274 AG+AA genotypes, rs2736340 CT+TT genotypes or rs4813003 TC+CC genotypes, respectively. Furthermore, a cumulative effect was observed with the ORs being gradually decreased with the increasing accumulative number of non-risk genotypes (Ptrend<0.001). In conclusion, our study suggests that 4 GWAS-identified SNPs, rs2736340, rs4813003, rs3818298 and rs1801274, were nominally associated with KD risk in a Han Chinese population individually and jointly.

CD32a polymorphism rs1801274 affects the risk of Kawasaki disease

“…For example, Khor and colleagues reported that the allele A of the polymorphism rs1801274 contributed to elevated KD risk [22], and similar findings have also been achieved by Onouch and colleagues [19]. Besides, Lou and colleagues exhibited nominally reducing tendency for AG þ GG vs. AA and GG vs. AA in their study [26]. While Kwon and colleagues claimed that significant correlation of the polymorphism with KD onset only appeared in males, not among females [29].…”

“…During the fulltext screening, 14 more publications were further omitted for not conforming to our inclusion criteria. As a result, 11 eligible reports were ultimately encompassed into this meta- analysis [19][20][21][22][23][24][25][26][27][28][29], containing 17 independent studies. Of the studies, 13 were on Asian populations while only 4 on Caucasians.…”

Prediction for Intravenous Immunoglobulin Resistance by Using Weighted Genetic Risk Score Identified From Genome-Wide Association Study in Kawasaki Disease

“… 23 Several genome-wide association studies have revealed common variants that strongly associated with KD, CAL formation, and IVIG treatment. 24 – 26 Here, we applied a GWAS-based weighted genetic risk score (wGRS) to develop a genetic model to predict the IVIG resistance in KD.…”

Use of corticosteroids during acute phase of Kawasaki disease

“…Although the efforts to find a causative microorganism have failed [2][3][4] , the suspicion of an association between some unidentified microorganism and Kawasaki disease remains [4][5][6][7] . Investigations to identify a genetic susceptibility locus in Kawasaki disease also have been performed recently [8][9][10] . Several institutes had cooperated and reported a result regarding the genetic susceptibility of Kawasaki disease [11] .…”