ArticleNature communications2023
Deciphering genetic causes for sex differences in human health through drug metabolism and transporter genes.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 4 of them syntheses that pooled it.
What it found
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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.
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Who cites it
47 citing papers in PubMed, 4 syntheses or guidelines pooled it, 103 citations in OpenAlex.
- Deciphering the role of oxidative stress genes in idiopathic pulmonary fibrosis: a multi-omics mendelian randomization approach.Genes and immunity · 2024Pooled it
- Dissecting the shared genetic landscape of anxiety, depression, and schizophrenia.Journal of translational medicine · 2024Pooled it
- Oxidative stress gene expression, DNA methylation, and gut microbiota interaction trigger Crohn's disease: a multi-omics Mendelian randomization study.BMC medicine · 2023Pooled it
- A systematic review on sex differences in adverse drug reactions related to psychotropic, cardiovascular, and analgesic medications.Frontiers in pharmacology · 2023Pooled it
- Sex Differences Between Female and Male Individuals in Antipsychotic Efficacy and Adverse Effects in the Treatment of Schizophrenia.CNS drugs · 2024Trial
- Mitochondrial Function-Related Genes in Sleep Disorders: A Multi-Omics Mendelian Randomization Study.Journal of molecular neuroscience : MN · 2026Article
- PharmVar GeneFocus: CYP1A2-Clinical Impact, Genetic Variation, and Updated Nomenclature.Clinical pharmacology and therapeutics · 2026Review
- Aortic valve stenosis serum IGFBP2 mediates female-specific Evogliptin resistance in valve myofibroblasts.Cell reports · 2026Article
- Deciphering the genetic underlying causes of sex differences in multiple myeloma incidence and mortality.HGG advances · 2026Article
- Sustained improvement in survival for primary ocular adnexal lymphoma from 2005 to 2024 by model-based period analysis.Discover oncology · 2026Article
- Macrophage polarization-related genes with potential causal roles in osteoporosis: a multi-omics Mendelian randomization study.Journal of orthopaedic surgery and research · 2026Article
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- Pharmacogenomics testing to optimize medical countermeasures against chemical warfare agents and bacterial biothreats in military settings.Journal of military, veteran and family health · 2026Article
- Deciphering the peripheral immune landscape of Alzheimer's disease through integrated multi-omics research and cohort validation.Frontiers in immunology · 2026Article
- Exploring Endoplasmic Reticulum Stress in Gestational Diabetes Mellitus: MultiOmics Insights Through Mendelian Randomization.International journal of women's health · 2026Article
- Sex differences in hepatic enzymes and transporters involved in pharmacokinetics.Liver research (Beijing, China) · 2025Review
- Genetic architecture and analysis practices of circulating metabolites in the NHLBI Trans-Omics for Precision Medicine Program.American journal of human genetics · 2025Article
- Sexual dimorphism in zebrafish liver proteins and implications for hepatic regeneration and diseases.Scientific reports · 2025Article
- A semi-empirical Bayes approach for calibrating weak instrumental bias in sex-specific Mendelian randomization studies.American journal of human genetics · 2025Article
- The role of circadian rhythm-related genes in type 2 diabetes from a multi-omics perspective.Journal of global health · 2025Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Sex differences have been widely observed in human health. However, little is known about the underlying mechanism behind these observed sex differences. We hypothesize that sex-differentiated genetic effects are contributors of these phenotypic differences. Focusing on a collection of drug metabolism enzymes and transporters (DMET) genes, we discover sex-differentiated genetic regulatory mechanisms between these genes and human complex traits. Here, we show that sex-differentiated genetic effects were present at genome-level and at DMET gene regions for many human complex traits. These sex-differentiated regulatory mechanisms are reflected in the levels of gene expression and endogenous serum biomarkers. Through Mendelian Randomization analysis, we identify putative sex-differentiated causal effects in each sex separately. Furthermore, we identify and validate sex differential gene expression of a subset of DMET genes in human liver samples. We observe higher protein abundance and enzyme activity of CYP1A2 in male-derived liver microsomes, which leads to higher level of an active metabolite formation of clozapine, a commonly prescribed antipsychotic drug. Taken together, our results demonstrate the presence of sex-differentiated genetic effects on DMET gene regulation, which manifest in various phenotypic traits including disease risks and drug responses.
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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.