Fig. 3: Genetic control of miRNA expression in malaria.
From: Integrative genomic analysis reveals mechanisms of immune evasion in P. falciparum malaria
a Manhattan plot of all associations tested between 276 miRNAs and 129,310 cis-SNPs. Associations implicating miR-4326, miR-1304-3p, and miR-598-3p are shown in green and in b–d, respectively. The associations shown are for SNPs spanning a 200-kb window centered on the miRNA in question. Peak SNPs are shown in green. The boxplots in b–d show miRNA expression and associated SNP data with host genotype (0, reference allele homozygote individuals versus 1/2, heterozygotes and alternative allele homozygote individuals (miR-4326/SNP rs6062431, miR-1304-3p/SNP rs10741471, and miR-598-3p/SNP rs114136945, n = 46). B–H FDR P values (linear regression model in PLINK v1.9) for each association are shown. e Association between parasitemia and SNP rs114136945 (left graph, nominal P value = 0.002, two-tailed student’s t test), miR-598-3p expression in the BI (n = 19) and SP (n = 17) groups (middle graph, B–H P = 4.15e-4, repeated measure ANCOVA), and right, correlation between miR-598-3p expression and log2 parasitemia in the replication set (n = 53, Pearson correlation coefficient r = 0.72, and P = 6.9e-7, multiple regression adjusting for sex, age, and white blood cell count). Each individual is colored by its log2 parasitemia (from the lowest (blue) to the highest (red). The box plots in b–e show the median, the 25th and 75th percentiles as box edges, and the 5th and 95th percentiles as bounds of whiskers. f Mediation analysis to evaluate potential causal relationship between SNP rs114136945 and log2 parasitemia through modulation of miR-598-3p expression. The regression coefficients β, their 95% confidence intervals and P values for each test are shown: β1 (−3.7), [−6.3, −1.1], P = 0.012, β2 (−1.5), P = 1.29e-3, β3, (−3.1), [−4.5, −1.4], P = 0.002 and β4 (−0.6), [−2.8, −0.9], P = 0.466.
