Computational protocol: UCP2 and UCP3 variants and gene-environment interaction associated with prediabetes and T2DM in a rural population: a case control study in China

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Protocol publication

[…] A set of SNPs with potential function were selected using SNP Function Prediction of SNPinfo Web Server. According to HapMap dbSNP (CHB/JPT population) and NCBI dbSNP (Asian), a chromosomal from 3000 bp upstream to 3000 bp downstream of UCP2 and UCP3 was searched, and 12 SNPs (rs45560234, rs632862, rs659366, rs660339, rs15763, rs1800006, rs1800849, rs2075577, rs590336, rs647126, rs7926165, rs7930460) were obtained with potential function and minor allele frequency (MAF) > 0.05. Furtherly, linkage disequilibrium (LD) TAG SNP Selection was used to select haplotype-tagging SNPs (tag SNPs). With the same searched chromosomal range and NCBI dbSNP (Asian), r2 ≥ 0.8, MAF ≥ 0.05 for SNPs having potential function, rs660339 and rs1800849 as the mandatory entry site due to function prediction and previous studies [–], three SNPs of UCP2 (rs660339, rs45560234 and rs643064) and six SNPs of UCP3 (rs7930460, rs15763, rs647126, rs1800849, rs3781907 and rs1685356) were selected for this study (Additional file : Table S1). [...] Data were described as mean ± standard deviation for continuous variables, and as frequencies (percentage) for non-continuous variables. Comparisons among the three groups were performed using one-way analyses of variance for continuous variables and χ2 test for categorical variables. Deviation from the Hardy-Weinberg equilibrium was assessed by χ2 test for the NGT group. Multinomial logistic regression analysis was performed to calculate crude odds ratios (ORs) and adjusted ORs (aORs) and their 95% confidential intervals (CIs). The genetic models tested in the study included additive, recessive and dominant models. Frequencies of haplotypes were calculated and compared among the three groups. Finally, we employed the general multifactor dimensionality reduction (GMDR) method [] and logistic regression to estimate the interaction between gene and environmental risk factors.Multinomial logistic regression, χ2 test and one-way analyses of variance were performed using SPSS version 19 software (Chicago, Illinois, USA). Haploview 4.2 and Hapstat3.0 were used to analyze linkage disequilibrium (LD) and haplotypes. GMDR software were used to estimate the interaction between gene and environmental factors. All tests were two-tailed, and it was considered statistically significant if a p value < 0.05 and marginally significant if a p value between 0.05 and 0.10. The Bonferroni for the number of SNPs was used to adjust the significance level of multiple comparisons when analyzing the association between genotypes and prediabetes or T2DM. […]

Pipeline specifications

Software tools SNPinfo, GMDR, Haploview
Databases dbSNP
Application GWAS