GENETIC SUSCEPTIBILITY LOCI IN GENOME-WIDE ASSOCIATION STUDY OF CLUSTER HEADACHE 125 6 Downstream bioinformatic analysis Using FUMA gene-based eQTL mapping, 16 genes were mapped to the four loci (Table 2). Additionally, gene-mapping with MAGMA identified five genes whose expression was significantly influenced by the CH loci, TMEM87B, MERTK, FHL5, UFL1 and ASZ1 (Figure 3). Finally, we performed a MAGMA tissue expression analysis which did not render any significant results (data not shown). Figure 2 Quantile-quantile (Q-Q) plot for association with cluster headache (CH) The horizontal axis shows -log10 p-values expected under the null distribution; The vertical axis shows observed -log10 p-values. Red = common SNPs (MAF ≥ 0.05), blue = low frequency SNPs (MAF = 0.005-0.05). Genomic inflation factor (λ) = 1.069. MAF = minor allele frequency RNA-seq analyses Using RNA-seq data from white blood cells of 39 CH patients and 20 controls we assessed the 16 eQTL-mapped genes derived from FUMA. Eleven genes were expressed in the samples, of which one was differentially lower expressed (POLR1B, p = 7.50 x 10-5, pcorr = 8.3 x 10-4) and one was nominally differentially lower expressed (TMEM87B, p = 0.014, pcorr = 0.15) in CH cases than in controls, both genes representing the rs6541998 locus (Table 5). The two genes were not differentially expressed in RNA-seq data when comparing 26 migraine with 20 controls (p = 0.50 and 0.45, respectively) (Table 5).
RkJQdWJsaXNoZXIy MTk4NDMw