SynthesisJAMA network open2023
Mendelian Randomization Analysis of Genetic Proxies of Thiazide Diuretics and the Reduction of Kidney Stone Risk.
Synthesis in JAMA network open, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 4 syntheses or guidelines pooled it, 39 citations in OpenAlex.
- Sleep traits and physical activity mediate the causal association between depression and age-related diseases.European archives of psychiatry and clinical neuroscience · 2026Pooled it
- Trans-ancestry GWAS identifies 59 loci and improves risk prediction and fine-mapping for kidney stone disease.Nature communications · 2025Pooled it
- The suggested dosage and course of thiazide diuretics on preventing recurrent urolithiasis: an upstate meta-analysis.World journal of urology · 2025Pooled it
- Pooled it
- Genetic causal association between kidney stones and proton pump inhibitors.International urology and nephrology · 2026Article
- Causal inference in psychiatric research: how to critically evaluate and interpret mendelian randomization studies.Molecular psychiatry · 2026Review
- Moving Mendelian Randomization From Traditional Risk Factors to Molecular Targets for Drug Development and Clinical Trials in Nephrology.Kidney international reports · 2026Review
- Calcium Phosphate Nephrolithiasis: A Comprehensive Review.Kidney medicine · 2026Review
- Lipid-lowering and glucose-lowering drug targets differentially modulate antipsychotic treatment efficacy in schizophrenia.Cell reports. Medicine · 2026Article
- A novel two-sample Mendelian randomization framework integrating common and rare variants: application to assess the effect of HDL-C on preeclampsia risk.Briefings in bioinformatics · 2026Article
- Causal Effect of Low-Density Lipoprotein Cholesterol on Chronic Kidney Disease: A Mendelian Randomization Study.Biochemistry research international · 2026Article
- Investigating the role of homocysteine and B vitamins in gestational diabetes mellitus: Mendelian randomization study.Nutrition journal · 2025Article
- Article
- Associations of genetic proxies for non-steroidal anti-inflammatory drugs with increased kidney stone risk: a Mendelian randomization study.Inflammopharmacology · 2025Article
- Genetic susceptibility to kidney stone disease: unveiling pathogenesis and potential therapeutic targets.The Journal of clinical investigation · 2025Article
- A flexible machine learning Mendelian randomization estimator applied to predict the safety and efficacy of sclerostin inhibition.American journal of human genetics · 2025Article
- The association of lipids and novel non-statin lipid-lowering drug target with osteoporosis: evidence from genetic correlations and Mendelian randomization.BMC musculoskeletal disorders · 2025Article
- Observational
- Article
- Inferring the genetic effects of serum homocysteine and vitamin B levels on autism spectral disorder through Mendelian randomization.European journal of nutrition · 2024Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Importance: Clinical trial data have called into question the efficacy of thiazide diuretics for the prevention of kidney stones. Objective: To identify whether there is an association between genetic proxies of thiazide diuretics and the risk of kidney stones. Design, Setting, and Participants: This genetic association study undertook a mendelian randomization analysis of derived exposures and outcomes from genome-wide association study summary statistics. Genetic proxies of thiazide diuretics were derived from the International Consortium for Blood Pressure. Kidney stone cases and controls were derived from the Million Veteran Program, UK Biobank, and the FinnGen study. These cross-sectional designs do not report a duration of follow-up. Data analysis was performed in May 2023. Exposure: Genetic proxies of thiazide diuretics were genetic variants in the thiazide-sensitive sodium chloride cotransporter gene associated with systolic blood pressure. Genetic proxies of β-blockers and systolic blood pressure served as negative controls. Main Outcomes and Measures: The main outcome was the odds of kidney stones. The secondary outcomes were serum laboratory values relevant to the treatment of kidney stones. Results: The main analysis included up to 1 079 657 individuals, including 50 832 kidney stone cases and 1 028 825 controls. In a meta-analysis of all cohorts, genetic proxies of thiazide diuretics were associated with a lower odds of kidney stones (OR, 0.85; 95% CI, 0.81-0.89; P < .001). Genetic proxies of β-blockers (OR, 1.02; 95% CI, 0.96-1.07; P = .52) and systolic blood pressure (OR, 1.00; 95% CI, 1.00-1.01; P = .49) were not associated with kidney stones. Genetic proxies of thiazide diuretics were associated with higher serum calcium (β [SE], 0.051 [0.0092]; P < .001) and total cholesterol (β [SE], 0.065 [0.015]; P < .001), but lower serum potassium (β [SE], -0.073 [0.022]; P < .001). Conclusions and Relevance: In this genetic association study, genetic proxies of thiazide diuretics were associated with reduced kidney stone risk. This finding reflects a drug effect over the course of a lifetime, unconstrained by the limited follow-up period of clinical trials.
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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.