Dataset Information

Validation of genome-wide associated variants for Kawasaki disease in a Taiwanese case-control sample.

ABSTRACT: Kawasaki disease (KD) is an acute febrile systemic vasculitis of unknown etiology that affects infants and young children. Considerable evidence supports the hypothesis that there is a genetic basis for KD susceptibility. Genome-wide association studies (GWAS) have identified several genetic variants associated with KD. This study aims to replicate three novel KD-associated single nucleotide polymorphisms (SNPs), identified by GWAS in Japanese, in a Taiwanese population. Associations between these SNPs and development of coronary artery lesions (CALs) were also investigated. The rs2254546 A/G, rs2857151 A/G, and rs4813003 C/T SNPs were genotyped in 681 children with KD and 563 ethnically-matched healthy controls using TaqMan Assay or DNA sequencing. We found rs2254546 and rs4813003 SNPs were significantly associated with KD (G allele, odds ratio [OR]?=?1.54, P?=?1.0?×?10-5; C allele, OR?=?1.32, P?=?8.1?×?10-4). However, no evidence for associations with CAL development was observed. Our study successfully validates associations of the rs2254546 and rs4813003 SNPs with KD in a Taiwanese population. Further functional studies of the SNPs are important in understanding the pathogenesis of KD.

SUBMITTER: Chen MR

PROVIDER: S-EPMC7366615 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Validation of genome-wide associated variants for Kawasaki disease in a Taiwanese case-control sample.

Chen Ming-Ren MR Chang Tzu-Yang TY Chiu Nan-Chang NC Chi Hsin H Yang Kuender D KD Chang Lung L Huang Daniel Tsung-Ning DT Huang Fu-Yuan FY Lien Ya-Ping YP Lin Wen-Shan WS Lin Chiung-Ling CL Chang Luan-Yin LY Lee Yann-Jinn YJ

Scientific reports 20200716 1

Kawasaki disease (KD) is an acute febrile systemic vasculitis of unknown etiology that affects infants and young children. Considerable evidence supports the hypothesis that there is a genetic basis for KD susceptibility. Genome-wide association studies (GWAS) have identified several genetic variants associated with KD. This study aims to replicate three novel KD-associated single nucleotide polymorphisms (SNPs), identified by GWAS in Japanese, in a Taiwanese population. Associations between the ...[more]

PMID: 32678208

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Project description:BACKGROUND:Large-scale genome-wide association studies have identified multiple genetic variants that are associated with elevated body mass index (BMI) or the risk of obesity in Caucasian or Asian populations. We examined whether these variants are individually associated with obesity in Chinese children, and also assessed their cumulative effects and predictive value for obesity risk in Chinese children. METHODS:We genotyped 40 single nucleotide polymorphisms (SNPs) and conducted association analyses for 32/40 SNPs with an estimated minor allele frequency >1% in 2 030 unrelated Chinese children, including 607 normal-weight, 718 overweight, and 705 obese individuals from two cross-sectional study groups. Logistic regression and linear regression under the additive model were used to examine associations, and the area under the receiver operating characteristic curve (AUCROC) was reported as prediction summary. RESULTS:We identified obesity association for 6 SNPs near SEC16B, RBJ, CDKAL1, TFAP2B, MAP2K5 and FTO (odds ratios (ORs) ranged from 1.19 to 1.41, nominal two-sided P-values < 0.05). Association (Bonferroni corrected) of rs543874 near SEC16B and rs2241423 near MAP2K5 had presumably stronger effects on obesity in Chinese children than in Caucasian populations. Their risk alleles were also associated with BMI standard deviation score (BMI-SDS) variability. We demonstrated the cumulative effects of the 32 SNPs on obesity risk (per risk allele: OR = 1.06, 95 % CI: 1.03-1.11, P = 4.84 × 10(-4)) and BMI-SDS (? = 0.04, 95% CI: 0.02-0.06, P = 3.69 × 10(-7)). The difference in AUCROC for a model with covariates (age, age square, sex and study group) and the model including covariates and all 32 SNPs was 2.8% (P = 0.0002). CONCLUSION:While six SNPs were individually associated with obesity in Chinese children, the 32 common variants identified by recent GWA studies had cumulative effects and resulted in a limited increase in the AUCROC predictive value for childhood obesity.

Project description:BACKGROUND:Brugada syndrome (BrS) is an oligogenic arrhythmic disease with increased risk of sudden cardiac arrest. Several BrS or ECG traits-related single-nucleotide polymorphisms (SNPs) were identified through previous genome-wide association studies in white patients. We aimed to validate these SNPs in BrS patients in the Taiwanese population, assessing the cumulative effect of risk alleles and the BrS-polygenic risk score in predicting cardiac events. METHODS:We genotyped 190 unrelated BrS patients using the TWB Array, and Taiwan Biobank was used as controls. SNPs not included in the array were imputed by IMPUTE2. Cox proportional hazards model was used to evaluate the associations between each particular SNP, the collective BrS-polygenic risk score, and clinical outcomes. RESULTS:Of the 88 previously reported SNPs, 22 were validated in Taiwanese BrS patients (P<0.05). Of the 22 SNPs, 2 (rs10428132 and rs9388451) were linked with susceptibility to BrS, 10 were SNPs previously reaching genome-wide significance, and 10 were SNPs associated with ECG traits. For the 3 most commonly reported SNPs, disease risk increased consistently with the number of risk alleles (odds ratio, 3.54; Ptrend=1.38×10-9 for 5 risk alleles versus 1). Similar patterns were observed in both SCN5A mutation+ (odds ratio, 3.66; Ptrend=0.049) and SCN5A mutation- (odds ratio, 3.75; Ptrend=8.54×10-9) subgroups. Furthermore, BrS patients without SCN5A mutations had more risk alleles than BrS patients with SCN5A mutations regardless of the range of polygenic risk scores. Three SNPs (rs4687718, rs7784776, and rs2968863) showed significant associations with the composite outcome (sudden cardiac arrest plus syncope, hazard ratio, 2.13, 1.48, and 0.41; P=0.02, 0.006, and 0.008, respectively). CONCLUSIONS:Our findings suggested that some SNPs associated with BrS or ECG traits exist across multiple populations. The cumulative risk of the BrS-related SNPs is similar to that in white BrS patients, but it appears to correlate with the absence of SCN5A mutations.

Dataset Information

Validation of genome-wide associated variants for Kawasaki disease in a Taiwanese case-control sample.

Publications

Validation of genome-wide associated variants for Kawasaki disease in a Taiwanese case-control sample.

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