Investigating pleiotropic effects of statins on ischemic heart disease in the UK Biobank using Mendelian randomisation
We examined whether specifically statins, of the major lipid modifiers (statins, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and ezetimibe) have pleiotropic effects on ischemic heart disease (IHD) via testosterone in men or women. As a validation, we similarly assessed whether a...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-08-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/58567 |
| _version_ | 1811252893949362176 |
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| author | CM Schooling JV Zhao SL Au Yeung GM Leung |
| author_facet | CM Schooling JV Zhao SL Au Yeung GM Leung |
| author_sort | CM Schooling |
| collection | DOAJ |
| description | We examined whether specifically statins, of the major lipid modifiers (statins, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and ezetimibe) have pleiotropic effects on ischemic heart disease (IHD) via testosterone in men or women. As a validation, we similarly assessed whether a drug that unexpectedly likely increases IHD also operates via testosterone. Using previously published genetic instruments we conducted a sex-specific univariable and multivariable Mendelian randomization study in the UK Biobank, including 179918 men with 25410 IHD cases and 212080 women with 12511 IHD cases. Of these three lipid modifiers, only genetically mimicking the effects of statins in men affected testosterone, which partly mediated effects on IHD. Correspondingly, genetically mimicking effects of anakinra on testosterone and IHD presented a reverse pattern to that for statins. These insights may facilitate the development of new interventions for cardiovascular diseases as well as highlighting the importance of sex-specific explanations, investigations, prevention and treatment. |
| first_indexed | 2024-04-12T16:42:22Z |
| format | Article |
| id | doaj.art-762b116be94c423f9a915c4cceda112b |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:42:22Z |
| publishDate | 2020-08-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-762b116be94c423f9a915c4cceda112b2022-12-22T03:24:44ZengeLife Sciences Publications LtdeLife2050-084X2020-08-01910.7554/eLife.58567Investigating pleiotropic effects of statins on ischemic heart disease in the UK Biobank using Mendelian randomisationCM Schooling0https://orcid.org/0000-0001-9933-5887JV Zhao1SL Au Yeung2GM Leung3School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; City University of New York, Graduate School of Public Health and Health Policy, New York, United StatesSchool of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, ChinaSchool of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, ChinaSchool of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, ChinaWe examined whether specifically statins, of the major lipid modifiers (statins, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and ezetimibe) have pleiotropic effects on ischemic heart disease (IHD) via testosterone in men or women. As a validation, we similarly assessed whether a drug that unexpectedly likely increases IHD also operates via testosterone. Using previously published genetic instruments we conducted a sex-specific univariable and multivariable Mendelian randomization study in the UK Biobank, including 179918 men with 25410 IHD cases and 212080 women with 12511 IHD cases. Of these three lipid modifiers, only genetically mimicking the effects of statins in men affected testosterone, which partly mediated effects on IHD. Correspondingly, genetically mimicking effects of anakinra on testosterone and IHD presented a reverse pattern to that for statins. These insights may facilitate the development of new interventions for cardiovascular diseases as well as highlighting the importance of sex-specific explanations, investigations, prevention and treatment.https://elifesciences.org/articles/58567statincardiovascularpleiotropysex-specifictestosterone |
| spellingShingle | CM Schooling JV Zhao SL Au Yeung GM Leung Investigating pleiotropic effects of statins on ischemic heart disease in the UK Biobank using Mendelian randomisation eLife statin cardiovascular pleiotropy sex-specific testosterone |
| title | Investigating pleiotropic effects of statins on ischemic heart disease in the UK Biobank using Mendelian randomisation |
| title_full | Investigating pleiotropic effects of statins on ischemic heart disease in the UK Biobank using Mendelian randomisation |
| title_fullStr | Investigating pleiotropic effects of statins on ischemic heart disease in the UK Biobank using Mendelian randomisation |
| title_full_unstemmed | Investigating pleiotropic effects of statins on ischemic heart disease in the UK Biobank using Mendelian randomisation |
| title_short | Investigating pleiotropic effects of statins on ischemic heart disease in the UK Biobank using Mendelian randomisation |
| title_sort | investigating pleiotropic effects of statins on ischemic heart disease in the uk biobank using mendelian randomisation |
| topic | statin cardiovascular pleiotropy sex-specific testosterone |
| url | https://elifesciences.org/articles/58567 |
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