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. 2021 Jan 5;17(1):241-244.
doi: 10.5114/aoms/127226. eCollection 2021.

PCSK9 genetic variants and cognitive abilities: a large-scale Mendelian randomization study

Donald M Lyall  1 , Joey Ward  1 , Maciej Banach  2 , George Davey Smith  3   4 , Jason G Gill  5 , Jill P Pell  1 , Michael V Holmes  3   6   7 , Naveed Sattar  5
Affiliations

PCSK9 genetic variants and cognitive abilities: a large-scale Mendelian randomization study

Donald M Lyall et al. Arch Med Sci. .

Abstract

Introduction: PCSK9 inhibitors lower low-density lipoprotein (LDL) cholesterol and are efficacious at reducing vascular disease, however questions remain about potential effects on cognitive function.

Methods: We examined the association of genetic variants in PCSK9 with continuous measures of cognitive ability in UK Biobank. Six independent polymorphisms in PCSK9 were used in up to 337,348 individuals.

Results: The PCSK9 allele score was associated with a lower risk of CHD, and weakly with worse log reaction time.

Conclusions: We are unable to rule out meaningful associations of PCSK9 genetic variants with cognition, emphasising the potential need for continued pharmacovigilance for patients currently treated with PCSK9 inhibitors.

Keywords: cardiovascular genomics; epidemiology; low-density lipoprotein.

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Conflict of interest statement

The Clinical Trial Service Unit and Epidemiological Studies Unit at the University of Oxford (MVH) has received research grants from Abbott/Solvay/Mylan, AstraZeneca, Bayer, GlaxoSmithKline, Merck, Novartis, Pfizer, Roche, and Schering. MVH has collaborated with Boehringer Ingelheim in research, and in accordance with the policy of the Clinical Trial Service Unit and Epidemiological Studies Unit (University of Oxford), did not accept any personal payment. NS has consulted for AstraZeneca, Bristol-Myers Squibb, Amgen, Sanofi, and Boehringer Ingelheim. All other authors have nothing to report.

Figures

Figure 1
Figure 1
Association of a PCSK9 allele score (in gray) scaled to 50 mg/dl lower LDL-cholesterol and other selected exposures (in black) with cognitive traits in UK Biobank
See this image and copyright information in PMC

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