de Ruiter, Sophie C.;
Schmidt, Floriaan;
Grobbee, Diederick E.;
den Ruijter, Hester M.;
Peters, Sanne A. E.;
(2023)
Sex-specific Mendelian randomisation to assess the causality of sex differences in the effects of risk factors and treatment: spotlight on hypertension.
Journal of Human Hypertension
10.1038/s41371-023-00821-1.
(In press).
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Abstract
Hypertension is a key modifiable risk factor for cardiovascular disease. Several observational studies have found a stronger association of blood pressure and cardiovascular disease risk in women compared to men. Since observational studies can be affected by sex-specific residual confounding and reverse causation, it remains unclear whether these differences reflect actual differential effects. Other study designs are needed to uncover the causality of sex differences in the strength of risk factor and treatment effects. Mendelian randomisation (MR) uses genetic variants as instrumental variables to provide evidence about putative causal relations between risk factors and outcomes. By exploiting the random allocation of genes at gamete forming, MR is unaffected by confounding and results in more reliable causal effect estimates. In this review, we discuss why and how sex-specific MR and cis-MR could be used to study sex differences in risk factor and drug target effects. Sex-specific MR can be helpful to strengthen causal inferences in the field of sex differences, where it is often challenging to distinguish nature from nurture. The challenge of sex-specific (drug target) MR lays in leveraging robust genetic instruments from sex-specific GWAS studies which are not commonly available. Knowledge on sex-specific causal effects of hypertension, or other risk factors, could improve clinical practice and health policies by tailoring interventions based on personalised risk. Drug target MR can help to determine the anticipated on-target effects of a drug compound and to identify targets to pursue in drug development
| Type: | Article |
|---|---|
| Title: | Sex-specific Mendelian randomisation to assess the causality of sex differences in the effects of risk factors and treatment: spotlight on hypertension |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41371-023-00821-1 |
| Publisher version: | https://doi.org/10.1038/s41371-023-00821-1 |
| Language: | English |
| Additional information: | © The Author(s) 2023 This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http:// creativecommons.org/licenses/by/4.0/. |
| Keywords: | Genetics research, Risk factors |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10168477 |
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