ArticleClinical pharmacology and therapeutics2026
Unraveling Novel Genetic Determinants of Thiopurine Response Via TWAS.
Article in Clinical pharmacology and therapeutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
- From Genotype to Functional Risk: A Multi-Omic Approach to Predicting Thiopurine and Methotrexate Co-Therapy-Induced Liver Injury.Pharmaceuticals (Basel, Switzerland) · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Thiopurines such as 6-mercaptopurine (6MP) are essential in ALL maintenance therapy. However, dose-limiting toxicities can significantly disrupt treatment. While genetic variants in TPMT and NUDT15 are known to affect thiopurine response, many patients with normal function genotypes in these genes still experience adverse effects, suggesting that additional genes might be involved. We analyzed 663 pediatric ALL patients enrolled in the AALL03N1 trial to identify novel genetic determinants of 6MP sensitivity, focusing on individuals with normal function TPMT and NUDT15 genotypes. A transcriptome-wide association study (TWAS) was conducted to focus on expression quantitative trait loci (eQTLs). Findings were validated in two independent cohorts: St. Jude Total Therapy XV (n = 390) and XVI (n = 552). TWAS identified 31 genes associated with 6MP dose intensity (q-value < 0.90). Of these, the imputed GNAQ expression was positively correlated with 6MP dose intensity and passed multiple testing thresholds in the validation cohorts. The rs60561071 variant, the eQTL in the GNAQ TWAS model, was associated with reduced gene expression and lower 6MP dose intensity. This study identifies GNAQ as a novel gene associated with thiopurine tolerance in ALL patients lacking known risk alleles in TPMT and NUDT15. Moreover, this research highlighted the innovative use of TWAS, providing deeper insights into the molecular mechanisms that explain drug response variability.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.