PCSK9 genetic variants and cognitive abilities: a large-scale Mendelian randomization study
Donald M Lyall1, Joey Ward1, Maciej Banach2
1Institute of Health and Wellbeing, University of Glasgow, Scotland, UK.
Archives of Medical Science : AMS
|January 25, 2021
Summary
Genetic variants in PCSK9 were studied for cognitive effects. While linked to lower cardiovascular risk, a weak association with slower reaction times suggests potential cognitive impacts warranting further study.
Area of Science:
- Genetics
- Neuroscience
- Pharmacology
Background:
- Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors effectively reduce low-density lipoprotein (LDL) cholesterol and vascular disease risk.
- However, the impact of PCSK9 inhibition on cognitive function remains an area of ongoing investigation.
Purpose of the Study:
- To investigate the association between genetic variants in PCSK9 and cognitive abilities.
- To assess potential links between PCSK9 genetic variations and cognitive performance in a large cohort.
Main Methods:
- Utilized UK Biobank data from up to 337,348 individuals.
- Examined six independent single nucleotide polymorphisms (SNPs) in the PCSK9 gene.
- Assessed the association of a PCSK9 allele score with continuous measures of cognitive ability.
Main Results:
- The PCSK9 allele score was significantly associated with a reduced risk of coronary heart disease (CHD).
- A weak association was observed between the PCSK9 allele score and worse log reaction time, indicating potential cognitive effects.
Conclusions:
- The study could not definitively exclude meaningful associations between PCSK9 genetic variants and cognitive function.
- These findings highlight the importance of continued pharmacovigilance for individuals receiving PCSK9 inhibitor therapy.
- Further research is needed to fully understand the relationship between PCSK9 modulation and cognitive health.
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