Fig. 2: Discovery of pharmacogenetic variants associated with AT-DILI.
From: Synergistic toxicity with copper contributes to NAT2-associated isoniazid toxicity
a Volcano plots showing the log2-transformed odds ratio (OR) on the x-axis and -log P value on the y-axis of the pharmacogenome-wide association study (PGxWAS) conducted in two different controls. The left panel shows the results from the comparison of 35 AT-DILI patients vs. 77 treatment-tolerant controls, and the right panel shows the results from the comparison of 35 AT-DILI patients vs. 1048 population controls. The ATP7B gene consistently showed the strongest signal in these comparisons. The orange and red dashed lines represent significance thresholds of P < 0.01 and P < 0.001, respectively. b Higher frequencies of NAT2 UAs were observed in AT-DILI patients than in treatment-tolerant controls in both the discovery (n = 112) and replication (n = 165) cohorts (OR 5.6 [2.5–13.2], P = 7.2 × 10−6). Furthermore, the combination of NAT2 UAs with ATP7B 832R/R occurred more frequently in AT-DILI patients (OR 32.5 [4.5–1423], P = 7.5 × 10−6; *P < 0.05; **P < 0.01; ***P < 0.001).
