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

Donald M. Lyall; Joey Ward; Maciej Banach; George Davey Smith; Jason M. R. 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

Donald M. Lyall^*, Joey Ward^*, Maciej Banach, George Davey Smith, Jason M. R. Gill, Jill P Pell, Michael V Holmes, Naveed Sattar^*

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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Abstract

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

Method: 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 worse log reaction time.

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

Original language	English
Pages (from-to)	241–244
Number of pages	4
Journal	Archives of Medical Science
Volume	17
Issue number	1
DOIs	https://doi.org/10.5114/aoms/127226
Publication status	Published - 5 Jan 2021

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© 2020 Termedia & Banach.

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IEU: MRC Integrative Epidemiology Unit Quinquennial renewal
Gaunt, L. F. (Principal Investigator) & Davey Smith, G. (Principal Investigator)
1/04/18 → 31/03/23
Project: Research

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title = "PCSK9 genetic variants and cognitive abilities: a large-scale Mendelian randomization study",

abstract = "Background: PCSK9 inhibitors lower low-density lipoprotein (LDL) cholesterol and are efficacious at reducing vascular disease, however questions remain about potential effects on cognitive function. Method: 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 worse log reaction time. Conclusion: We are unable to rule out meaningful associations of PCSK9 genetic variants with cognition, emphasising continued pharmacovigilance for patients currently treated with PCSK9 inhibitors.",

author = "Lyall, {Donald M.} and Joey Ward and Maciej Banach and {Davey Smith}, George and Gill, {Jason M. R.} and Pell, {Jill P} and Holmes, {Michael V} and Naveed Sattar",

note = "Publisher Copyright: {\textcopyright} 2020 Termedia & Banach.",

year = "2021",

month = jan,

day = "5",

doi = "10.5114/aoms/127226",

language = "English",

volume = "17",

pages = "241–244",

journal = "Archives of Medical Science",

issn = "1734-1922",

publisher = "Termedia Publishing House Ltd.",

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TY - JOUR

T1 - PCSK9 genetic variants and cognitive abilities

T2 - a large-scale Mendelian randomization study

AU - Lyall, Donald M.

AU - Ward, Joey

AU - Banach, Maciej

AU - Davey Smith, George

AU - Gill, Jason M. R.

AU - Pell, Jill P

AU - Holmes, Michael V

AU - Sattar, Naveed

PY - 2021/1/5

Y1 - 2021/1/5

N2 - Background: PCSK9 inhibitors lower low-density lipoprotein (LDL) cholesterol and are efficacious at reducing vascular disease, however questions remain about potential effects on cognitive function. Method: 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 worse log reaction time. Conclusion: We are unable to rule out meaningful associations of PCSK9 genetic variants with cognition, emphasising continued pharmacovigilance for patients currently treated with PCSK9 inhibitors.

AB - Background: PCSK9 inhibitors lower low-density lipoprotein (LDL) cholesterol and are efficacious at reducing vascular disease, however questions remain about potential effects on cognitive function. Method: 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 worse log reaction time. Conclusion: We are unable to rule out meaningful associations of PCSK9 genetic variants with cognition, emphasising continued pharmacovigilance for patients currently treated with PCSK9 inhibitors.

U2 - 10.5114/aoms/127226

DO - 10.5114/aoms/127226

M3 - Article (Academic Journal)

C2 - 33488877

SN - 1734-1922

VL - 17

SP - 241

EP - 244

JO - Archives of Medical Science

JF - Archives of Medical Science

IS - 1

ER -

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

Abstract

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IEU: MRC Integrative Epidemiology Unit Quinquennial renewal

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