ArticleSSM - population health2019
Reproduction and longevity: A Mendelian randomization study of gonadotropin-releasing hormone and ischemic heart disease.
Article in SSM - population health, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Appraising the Causal Role of Risk Factors in Coronary Artery Disease and Stroke: A Systematic Review of Mendelian Randomization Studies.Journal of the American Heart Association · 2023Pooled it
- Genetic Evidence Supporting a Causal Association Between mTORC1-Dependent Circulating Protein Levels and Diabetic Retinopathy.Translational vision science & technology · 2025Article
- Day-night and seasonal variation of human gene expression across tissues.PLoS biology · 2023Article
- Shared genetics and causal relationships between major depressive disorder and COVID-19 related traits: a large-scale genome-wide cross-trait meta-analysis.Frontiers in psychiatry · 2023Article
- Association of mTORC1‑dependent circulating protein levels with cataract formation: a mendelian randomization study.BMC genomics · 2022Article
- Investigating the effects of statins on ischemic heart disease allowing for effects on body mass index: a Mendelian randomization study.Scientific reports · 2022Article
- Day-night and seasonal variation of human gene expression across tissues.bioRxiv : the preprint server for biology · 2022Article
- Joint Analysis of Genome-Wide Association Data Reveals No Genetic Correlations Between Low Back Pain and Neurodegenerative Diseases.Frontiers in genetics · 2021Article
- Causal association between mTOR-dependent EIF-4E and EIF-4A circulating protein levels and type 2 diabetes: a Mendelian randomization study.Scientific reports · 2020Article
- Article
- Indoleamine 2,3-dioxygenase and ischemic heart disease: a Mendelian Randomization study.Scientific reports · 2019Article
- Sex-specific Mendelian randomization study of genetically predicted insulin and cardiovascular events in the UK Biobank.Communications biology · 2019Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAccording to well-established evolutionary biology theory there is a trade-off between reproduction and longevity, implying that upregulating the reproductive axis might drive major diseases. We assessed whether the central driver of reproduction gonadotropin-releasing hormone 1 (GnRH1) had a causal effect on the leading cause of global morbidity and mortality, i.e. ischemic heart disease (IHD). As a contrast we similarly examined the role of GnRH2 because it is more a driver of female sexual behavior.
methodsWe applied strong (p-value <5 × 10
findingsGnRH1, predicted by 11 genetic variants, was positively associated with IHD (IVW odds ratio (OR) 1.04 per effect size, 95% confidence interval (CI) 1.01 to 1.08), but GnRH2, predicted by 15 genetic variants, was not (IVW OR 0.98, 95% CI 0.95 to 1.02). Estimates from sensitivity analysis were similar.
interpretationGnRH1 is a potential IHD genetic target. Apart from demonstrating a central tenet of evolutionary biology in humans, our study suggests that existing treatments and environmental factors targeting GnRH1, its drivers or consequences could be re-purposed to prevent and treat IHD. Given, the importance of reproduction to the human species, many such exposures likely exist.
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