Computational protocol: Genome-wide association study identifies susceptibility loci for Dengue shock syndrome at MICB and PLCE1

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Protocol publication

[…] Stringent QC filters were applied to remove poorly performing SNPs and samples using tools implemented in PLINK version 1.7 . The QC criteria were as follows: SNPs that had > 5% of missing genotypes, gross departure from Hardy-Weinberg equilibrium (test for HWE showing P < 10−7) or were of minor allele frequency below 1% were excluded from downstream analysis. For sample QC, samples with an overall genotyping call rate of < 95% were excluded from analysis. The remaining samples were then subjected to biological relationship verification by using the principle of variability in allele sharing according to the degree of relationship. Identity-by-state (IBS) information was derived using PLINK. For those pairs of individuals who showed evidence of cryptic relatedness (possibly either due to duplicated or biologically related samples), we removed the sample with the lower call rate before performing principal component (PC) analysis. PC analysis was undertaken to account for spurious associations resulting from ancestral differences of individual SNPs , and PC plots were performed using the R statistical program package (R-project, see URLs).For both the GWAS and replication stages, analysis of association with DSS was carried out using a 1 degree of freedom (d.f.) score-based test. This test models for a trend-per-copy of the minor allele on disease risk and has been extensively described -. It has the best statistical power to detect association for complex traits across a wide range of alternative hypotheses, with the exception of those involving rare recessive variants . The threshold for significant independent replication was set at P < 0.05 in the combined replication data sets .Meta-analysis was conducted using inverse variance weights for each cohort, which calculates an overall Z-statistic, corresponding P-value and accompanying odds ratios for each SNP analyzed -. Genotyping clusters were directly visualized for the 85 SNPs exceeding P < 10−4 and confirmed to be of good quality before inclusion for statistical analysis. shows the cluster plots for MICB rs3132468 and PLCE1 rs3740360, the two SNPs with showing P < 10−7 in the GWAS stage. Analysis of linkage disequilibrium was performed using Haploview . […]

Pipeline specifications

Software tools PLINK, Haploview
Application GWAS
Organisms Homo sapiens
Diseases Severe Dengue