Genotype-derived interpretive categories of drug response in 908 pharmacogenomic reports from Chinese patients with type 2 diabetes: A retrospective single-centre study
- 1Department of Geriatrics, Shandong Zaozhuang Municipal Hospital, Zaozhuang, Shandong, China
- 2Department of Endocrinology, Shandong Health Group Zaozhuang Central Hospital, Zaozhuang, Shandong, China
- 3Department of Urology, Shandong Zaozhuang Municipal Hospital, Zaozhuang, Shandong, China
Abstract
Pharmacogenomic testing is increasingly ordered in routine diabetes care, but the reports it generates are heterogeneous and are not in a form that can be analysed systematically. We examined how genotype is translated into interpretive categories of drug response in a real-world Chinese cohort, and how consistently that translation is applied. We analysed 908 de-identified pharmacogenomic reports issued for patients with type 2 diabetes at a single centre between July 2022 and April 2024. An interpretation rulebook, taken from the standing appendix that the testing laboratory attached to every report and completed by reconstructing the rules that appendix does not state, mapped six single-nucleotide polymorphisms onto eight genotype-derived interpretive categories. These are classifications, not measured outcomes: no glycaemic response, hypoglycaemia, adverse event, treatment discontinuation or dose modification was recorded, so no category could be checked against outcome. Allele frequencies matched gnomAD East Asian data except at the risk loci, where the risk alleles were enriched, as expected in a case-only cohort. Each pre-defined variant was the statistical driver of its corresponding category, with odds ratios inflated by quasi-complete separation because the coding rules are deterministic. Across 5,983 category assignments the rulebook reproduced 5,940 (99.3%), leaving 43 discordant assignments in 28 reports; a structured audit makes most of them consistent with a mismatch between the genotype printed on a report and the genotype its interpretation was generated from. The sulfonylurea efficacy category was assigned by two different rules over the study period, and the “increased efficacy” level appeared only in reports from the later, six-locus panel, where it tracked reduced-function CYP2C9 genotypes. Nothing in the report indicated which rule had been applied. Interpretation drifts as assays are revised, and writing the rulebook down and versioning it is what makes that drift visible.
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BibTeX
@article{liu2026genotypederived,
title = {{Genotype-derived interpretive categories of drug response in 908 pharmacogenomic reports from Chinese patients with type 2 diabetes: A retrospective single-centre study}},
author = {Ye Liu and Chun-xiao Yu and Li Lu},
journal = {PLOS One},
year = {2026},
month = nov,
doi = {10.1371/journal.pone.0351903},
url = {https://doi.org/10.1371/journal.pone.0351903},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Genotype-derived interpretive categories of drug response in 908 pharmacogenomic reports from Chinese patients with type 2 diabetes: A retrospective single-centre study
AU - Ye Liu
AU - Chun-xiao Yu
AU - Li Lu
PY - 2026
DA - 2026/11/05
JO - PLOS One
DO - 10.1371/journal.pone.0351903
UR - https://doi.org/10.1371/journal.pone.0351903
AB - Pharmacogenomic testing is increasingly ordered in routine diabetes care, but the reports it generates are heterogeneous and are not in a form that can be analysed systematically. We examined how genotype is translated into interpretive categories of drug response in a real-world Chinese cohort, and how consistently that translation is applied. We analysed 908 de-identified pharmacogenomic reports issued for patients with type 2 diabetes at a single centre between July 2022 and April 2024. An interpretation rulebook, taken from the standing appendix that the testing laboratory attached to every report and completed by reconstructing the rules that appendix does not state, mapped six single-nucleotide polymorphisms onto eight genotype-derived interpretive categories. These are classifications, not measured outcomes: no glycaemic response, hypoglycaemia, adverse event, treatment discontinuation or dose modification was recorded, so no category could be checked against outcome. Allele frequencies matched gnomAD East Asian data except at the risk loci, where the risk alleles were enriched, as expected in a case-only cohort. Each pre-defined variant was the statistical driver of its corresponding category, with odds ratios inflated by quasi-complete separation because the coding rules are deterministic. Across 5,983 category assignments the rulebook reproduced 5,940 (99.3%), leaving 43 discordant assignments in 28 reports; a structured audit makes most of them consistent with a mismatch between the genotype printed on a report and the genotype its interpretation was generated from. The sulfonylurea efficacy category was assigned by two different rules over the study period, and the “increased efficacy” level appeared only in reports from the later, six-locus panel, where it tracked reduced-function CYP2C9 genotypes. Nothing in the report indicated which rule had been applied. Interpretation drifts as assays are revised, and writing the rulebook down and versioning it is what makes that drift visible.
SN - 1932-6203
ER -