Computational protocol: Favourable IFNL3 Genotypes Are Associated with Spontaneous Clearance and Are Differentially Distributed in Aboriginals in Canadian HIV-Hepatitis C Co-Infected Individuals

Similar protocols

Protocol publication

[…] The software PHASE v2.1 was used for haplotype inference and distribution [,]. Haploview [] and Stata version 12 were used to determine allele frequency distributions, Hardy-Weinberg Equilibrium measures, and linkage disequilibrium (LD) measures in Aboriginals and Canadian-born whites. Pearson’s Chi-squared test was used to compare allelic and genotypic frequencies between the two subpopulations. The Stata command-hapipf- was used to test presence of LD in each group and also compare haplotypic frequencies between the two.Due to the presence of censoring and left truncation, data were analyzed using Cox proportional hazards with adjustments for sex and ethnicity. The time axis was calendar time with the estimated date of HCV infection as the origin. Time in the analysis for each patient starts with cohort entry. This method of late entry was used to address the problem of left truncation since half the Cohort had been HCV infected for over 18 years at first visit. HCV duration was estimated based on date of HCV seroconversion, if known, or on the year of first injection drug use or blood product exposure. Interaction terms were tested between the IFNL3 genotype and sex as such interactions have previously been reported []. Due to the absence of HCV RNA in some available samples, HCV genotype information was missing in approximately 20% of the study population. Thus, HCV genotype was not included in the main multivariate analysis. In sensitivity analyses, Multiple Imputation by Chained Equations (MICE) was used to impute missing HCV genotypes []. Missingness for HCV genotype and other variables such as RNA tests, plasma samples, or IFNL3 genotype was assumed to be at random. Stata 12 was used for all analyses (StataCorp LP, College Station, TX, USA).A dominant model was used in the association analyses between genotype and spontaneous clearance. Subjects with one or two copies of the variant allele were grouped and contrasted with the wild-type genotype. For all three SNPs the homozygous wild-type genotype is considered favourable. Therefore, for rs12979860, genotype CC was compared with the CT and TT genotypes, whereas for rs8099917 and rs8103142 the TT genotype was compared with the TG and GG genotypes or with the TC and CC genotypes, respectively.For the haplotype analysis, the Stata command-haplologit- was used to test the effect of TCT, the haplotype with the favourable alleles at all the SNPs (T at rs8103142, C at rs12979860 and T at rs8099917), after adjusting for ethnicity. […]

Pipeline specifications

Software tools Haploview, Stata, IMPUTE
Application GWAS
Organisms Classical swine fever virus
Diseases Hepatitis C, HIV Infections, Coinfection
Chemicals Interferons