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

Donald M Lyall; Joey Ward; Maciej Banach; George Davey Smith; Jason G Gill; Jill P Pell; Michael V Holmes; Naveed Sattar

doi:10.5114/aoms/127226

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

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

Authors

Donald M Lyall¹, Joey Ward¹, Maciej Banach², George Davey Smith^{3

4}, Jason G Gill⁵, Jill P Pell¹, Michael V Holmes^{3

6

7}, Naveed Sattar⁵

Affiliations

¹ Institute of Health and Wellbeing, University of Glasgow, Scotland, UK.
² Department of Hypertension, Medical University of Lodz, Lodz, Poland.
³ Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
⁴ School of Social and Community Medicine, University of Bristol, Bristol, UK.
⁵ Institute of Cardiovascular and Medical Sciences, University of Glasgow, Scotland, UK.
⁶ Medical Research Council Population Health Research Unit at the University of Oxford, Oxford, UK.
⁷ National Institute for Health Research, Oxford Biomedical Research Centre, Oxford University Hospital, Oxford, UK.

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.

Abstract

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