FIGURE 4.
Genome‐wide single nucleotide polymorphism (SNP) and gene‐based association studies of cisplatin‐induced tinnitus. (A) Manhattan plot of genome‐wide association study (GWAS) results for cisplatin‐induced tinnitus. (B) Quantile–Quantile plot of GWAS results for cisplatin‐induced tinnitus. Covariates in the GWAS include cumulative cisplatin dose, noise exposure, age at clinical evaluation, and five European genetic principal components accounting for population substructure. (C) Manhattan plot of the gene‐based association analysis identifies WNT8A (p = 2.5 × 10−6) as genome‐wide significant. Summary statistics for SNP‐based GWAS were uploaded to functional mapping and annotation to run a gene‐based association analysis based on a multiple linear principal components regression to determine the aggregated effect of all SNPs within a gene. Inputted SNPs were mapped to 18,819 protein coding genes, producing a significance threshold of p = 0.05/18,819 (2.7 × 10−6). (D) Quantile–Quantile plot of results from the gene‐based association analysis