Computational protocol: MicroRNA-3148 Modulates Allelic Expression of Toll-Like Receptor 7 Variant Associated with Systemic Lupus Erythematosus

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Protocol publication

[…] Imputation was performed at 12.86–12.95 Mb on Xp22.2 using IMPUTE 2.1.2 , with SNP/INDEL genotypes of 381 Europeans, 246 Africans and 181 Americans from the 1000 Genomes Project (“version 3” of the Phase 1 integrated data, March 2012 release) as references in imputation for our EA, AA and HS subjects, respectively. Imputed genotypes had to meet information score of >0.9, as well as the quality control criteria as described above. After imputation, we obtained an additional 75 variants for EA, 57 for AA and 63 for HS (the number varied based on LD structure) for further analysis. [...] Associations of SNPs with SLE were assessed in each ancestral group under a logistic regression model adjusted for gender and the first three principal components estimated using AIMs. Conditional haplotype-based association tests were also performed by adjusting for gender and the first three principal components. The trans-ancestral meta-analysis was conducted on 40 genotyped and 14 imputed SNPs that were shared by the three ancestries with both a fixed and random-effects model. Homogeneity of odds ratios was evaluated using Cochrane's Q test. For each SNP, if the Cochran's Q test showed no evidence of genetic heterogeneity (P>0.05), a fixed-effects model was implemented; otherwise, a random-effects model was used. The Bonferroni corrected P-value threshold was adjusted to P<9.1×10−4 on the basis of the maximum number of tests across all populations (55 independent variants with r2<0.8). All analyses described above were performed using PLINK v1.07. Pairwised LD values shown in and were calculated using Haploview 4.2. Other data were analyzed using GraphPad Prism 4.0 software. A P value<0.05 was considered to be statistically significant. […]

Pipeline specifications

Software tools IMPUTE, PLINK, Haploview
Application GWAS
Organisms Homo sapiens
Diseases Lupus Erythematosus, Systemic