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01-12-2021 | Statins | Research article

A phenome-wide association study of genetically mimicked statins

Authors: Shun Li, C. M. Schooling

Published in: BMC Medicine | Issue 1/2021

Abstract

Background

Beyond their success in cardiovascular disease prevention, statins are increasingly recognized to have sex-specific pleiotropic effects. To gain additional insight, we characterized associations of genetically mimicked statins across the phenotype sex-specifically. We also assessed whether any apparently non-lipid effects identified extended to genetically mimicking other widely used lipid modifiers (proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and ezetimibe) or were a consequence of low-density lipoprotein cholesterol (LDL-c).

Methods

We performed a sex-specific phenome-wide association study assessing the association of genetic variants in HMGCR, mimicking statins, with 1701 phenotypes. We used Mendelian randomization (MR) to assess if any non-lipid effects found were evident for genetically mimicked PCSK9 inhibitors and ezetimibe or for LDL-c.

Results

As expected, genetically mimicking statins was inversely associated with LDL-c, apolipoprotein B (ApoB), and total cholesterol (TC) and positively associated with glycated hemoglobin (HbA1c) and was related to body composition. Genetically mimicking statins was also inversely associated with serum calcium, sex hormone-binding globulin (SHBG), and platelet count and positively associated with basal metabolic rate (BMR) and mean platelet volume. Stronger associations with genetically mimicked statins were evident for women than men for lipid traits (LDL-c, ApoB, and TC), calcium, and SHBG, but not for platelet attributes, body composition, or BMR. Genetically mimicking PCSK9 inhibitors or ezetimibe was also associated with lower lipids, but was not related to calcium, SHBG, BMR, or body composition. Genetically higher LDL-c increased lipids and decreased BMR, but did not affect calcium, HbA1c, platelet attributes, or SHBG with minor effects on body composition.

Conclusions

Similar inverse associations were found for genetically mimicking statins on lipid traits in men and women as for other lipid modifiers. Besides the positive associations with HbA1c, BMI (which may explain the higher BMR), and aspects of body composition in men and women, genetically mimicking statins was additionally associated with platelet attributes in both sexes and was inversely associated with serum calcium and SHBG in women. This genetic evidence suggests potential pathways that contribute to the effects of statins particularly in women. Further investigation is needed to confirm these findings and their implications for clinical practice.

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Title: A phenome-wide association study of genetically mimicked statins
Authors: Shun Li
C. M. Schooling
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Statins
PCSK9 Inhibitor
Ezetimibe
Published in: BMC Medicine / Issue 1/2021
Electronic ISSN: 1741-7015
DOI: https://doi.org/10.1186/s12916-021-02013-5

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

A phenome-wide association study of genetically mimicked statins

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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