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

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.