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bioRxiv · 10.1101/472548

Reproduction and longevity A Mendelian randomization study of gonadotropin-releasing hormone and ischemic heart disease

Schooling, C.·Ng, J.
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Abstract

BackgroundAccording to well-established evolutionary biology theory reproduction trades-off against 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.\n\nMethodsWe applied strong (p-value <5x10-6) and independent genetic predictors of GnRH1 and GnRH2 to an extensively genotyped IHD case (n=76,014) - control (n=264,785) study using multiplicative random effects inverse variance weighted (IVW), weighted median, MR-Egger and MR-PRESSO estimates.\n\nResultsGnRH1, 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).\n\nConclusionsGnRH1 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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Schooling, C., Ng, J.. 2018-11-19. Reproduction and longevity A Mendelian randomization study of gonadotropin-releasing hormone and ischemic heart disease. https://doi.org/10.1101/472548

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