Evidence map›Paper›PMID 41646817›Full record

ArticlemedRxiv : the preprint server for health sciences2026

Pharmacogenomic predictors of drug response and choice in dyslipidemia and hypertension.

Fumihiko Takeuchi, Malathi S I Dona, William W H Ho, Samuel A Lambert, Michael Inouye, Norihiro Kato

Abstract readPreprint
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
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0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Fumihiko TakeuchiDepartment of Bioinformatics, National Institute of Global Health and Medicine, Japan Institute for Health Security, Tokyo, Japan.ORCID 0000-0003-3185-5661
Malathi S I DonaCambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, Australia.
William W H HoCambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, Australia.
Samuel A LambertCambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, Australia.
Michael InouyeCambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, Australia.
Norihiro KatoMedical Genomics Center, National Institute of Global Health and Medicine, Japan Institute for Health Security, Tokyo, Japan.

Funding

Strengthening community knowledge bases for genetic association studies and polygenic scores, the GWAS and PGS CatalogsU24HG012542 · NHGRI · EUROPEAN MOLECULAR BIOLOGY LABORATORY · PI Michael Inouye, Helen Elizabeth Parkinson · 2022 to 2026
$5.2M
NHGRI NIH HHS U24 HG012542
6 · The paper itself

Abstract

Background: Drug suitability is determined by safety, efficacy, and pathological appropriateness. The pharmacogenomics of drug suitability can be assessed by analyzing drug response and drug choice in large population cohorts. Methods: We investigated drug response and drug choice for dyslipidemia and hypertension using genetic, phenotypic, and prescribing data from the UK Biobank and the All of Us Research Program. Drug response was reassessed with rigorous biomarker scaling, while genome-wide association studies (GWAS) and polygenic scores were used to examine genetic factors influencing drug choice. Results: Conventional analyses showed that variants influencing baseline LDL cholesterol (LDL-C) were inversely associated with absolute LDL-C change but concordant with relative change following statin therapy; these signals disappeared after applying a variance-stabilizing Box-Cox transformation, indicating a methodological artifact in biomarker scaling. GWAS for drug choice identified several significant loci and unique genetic correlation patterns with cardiometabolic traits. Polygenic scores for drug choice yielded statistically significant predictive performance, which was enhanced by incorporating demographic factors, though prediction strength in clinical settings remains modest. Conclusion: Variance-stabilizing transformation corrects spurious pharmacogenetic associations introduced by biomarker scaling. Genetic variation informs drug choice for dyslipidemia and hypertension, but current polygenic scores provide only modest benefits in clinical application.

Indexed as

Box-Cox transformationcardiometabolic traitsdrug choicedrug efficacydyslipidemiagenome-wide association studyhypertensionpharmacogenomicspolygenic score

Identifiers

PMID41646817
PMCPMC12870588

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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.