Computational protocol: Associations of epithelial sodium channel genes with blood pressure: the GenSalt study

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Protocol publication

[…] SCNN1A, SCNN1G and SCNN1B genes were identified based on their potential biological effect on BP regulation. Seventeen SNPs were genotyped using ABI SNPlex platform (Applied Biosystems, Foster City, CA) and additional 42 SNPs were genotyped on the Affymetrix 6.0 platform (Affymetrix, Santa Clara, CA) in a subsample of GenSalt participants (N=1,881). SNPs with minor allele frequency (MAF) less than 1%, genotyping call rate less than 90% and deviation from Hardy-Weinberg equilibrium (HWE) after Bonferroni correction for multiple testing were excluded. After quality control, we selected tag-SNPs from these genes with pairwise r2 thresholds of less than 0.9. A total of 44 tag-SNPs were included in the current analysis. Haploview software (version 4.2, was used to conduct quality control and tag-SNPs selection. Detailed information on all tag-SNPs, including the gene symbol, chromosome, physical position, major/minor alleles, call rate, MAF, HWE P value and genotyping platform, has been shown in . [...] The Mendelian consistency of the SNP genotype data was assessed by PLINK software ( and PedCheck. , If Mendelian inconsistencies were found, genotypes for related SNPs in those families were set to be missing. Baseline characteristics and BP were presented as mean±SD for continuous variables and as percentages for categorical variables. Mixed-effect linear models were used to assess associations of SNPs with BP to account for the non-independence of family members under additive, codominant, dominant, and recessive genetic models. Age, gender, BMI, room temperature of BP measurement, and field center were adjusted in the mixed models. All single-marker analyses were conducted using SAS statistical software (version 9.2, SAS Institute, Cary, NC).The truncated product method (TPM), which combines P values from single-marker association analyses, was used to evaluate the overall association of a candidate gene with BP levels. Truncation point was set as τ=0.10, and the P value for TPM was estimated by 1,000,000 simulations. Sensitivity analyses were conducted using the TPM after excluding the most significant SNP within a gene. Gene-based gene-gene interaction was evaluated by GG_tProd method by combining P values from single-marker based interaction term under additive model. Gene-based analyses and Gene-based gene-gene interaction were performed using R software (Version 3.0.1; correction was used to adjust for multiple testing. The α-thresholds were 1.14×10−3 (0.05/44) and 0.017 (0.05/3) for single-marker analyses and gene-based analyses, respectively. […]

Pipeline specifications

Software tools Haploview, PLINK, PedCheck
Application GWAS
Organisms Homo sapiens
Diseases Hypotension