Genetic analysis of the PCSK9 locus in psychological, psychiatric, metabolic and cardiovascular traits in UK Biobank

The association between severe mental illness (SMI) and cardiovascular and metabolic disease (CMD) is poorly understood. PCSK9 is expressed in systems critical to both SMI and CMD and influences lipid homeostasis and brain function. We systematically investigated relationships between genetic variat...

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Bibliographic Details
Published in:European journal of human genetics : EJHG 2022-12, Vol.30 (12), p.1380-1390
Main Authors: Hay, Rachel, Cullen, Breda, Graham, Nicholas, Lyall, Donald M, Aman, Alisha, Pell, Jill P, Ward, Joey, Smith, Daniel J, Strawbridge, Rona J
Format: Article
Language:English
Subjects:
Adipose tissue
Biobanks
Biological Specimen Banks
Blood pressure
Cardiovascular Diseases - genetics
Cardiovascular Diseases - pathology
Embolism
Genetic analysis
Genetic diversity
Genome-Wide Association Study
Homeostasis
Humans
Linkage disequilibrium
Lipids
Mental disorders
Metabolic disorders
Metabolism
Mood
Neurosis
Phenotype
Phenotypes
Polymorphism, Single Nucleotide
Proprotein Convertase 9 - genetics
Single-nucleotide polymorphism
Thrombosis
United Kingdom
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Summary:The association between severe mental illness (SMI) and cardiovascular and metabolic disease (CMD) is poorly understood. PCSK9 is expressed in systems critical to both SMI and CMD and influences lipid homeostasis and brain function. We systematically investigated relationships between genetic variation within the PCSK9 locus and risk for both CMD and SMI. UK Biobank recruited ~500,000 volunteers and assessed a wide range of SMI and CMD phenotypes. We used genetic data from white British ancestry individuals of UK Biobank. Genetic association analyses were conducted in PLINK, with statistical significance defined by the number of independent SNPs. Conditional analyses and linkage disequilibrium assessed the independence of SNPs and the presence of multiple signals. Two genetic risk scores of lipid-lowering alleles were calculated and used as proxies for putative lipid-lowering effects of PCSK9. PCSK9 variants were associated with central adiposity, venous thrombosis embolism, systolic blood pressure, mood instability, and neuroticism (all p 
ISSN:1018-4813
1476-5438
DOI:10.1038/s41431-022-01107-9