Genetic variants associated with altered plasma levels of c-reactive protein are not associated with late-life cognitive ability in four Scottish samples

Riccardo E. Marioni, Ian J. Deary, Gordon D. Murray, Gordon D. O. Lowe, Snorri B. Rafnsson, Mark W. J. Strachan, Michelle Luciano, Lorna M. Houlihan, Alan J. Gow, Sarah E. Harris, Marlene C. Stewart, Ann Rumley, F. Gerry R. Fowkes, Jackie F. Price

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    Abstract

    It is unknown whether the relationship between raised inflammatory biomarker levels and late-life cognitive ability is causal. We explored this issue by testing the association between genetic regulators of plasma C-reactive protein (CRP) and cognition. Data were analysed from four cohorts based in central Scotland (Total N = 4,782). Associations were tested between variants in the CRP gene and both plasma CRP levels and a battery of neuropsychological tests, including a vocabulary-based estimate of peak prior cognitive ability and a general (summary) cognitive factor score, or 'g'. CRP levels were associated with a number of variants in the CRP gene (SNPs), including rs1205, rs1130864, rs1800947, and rs1417938 (P range 4.2e-06 to 0.041). Higher CRP levels were also associated with vocabulary-adjusted cognitive ability, used here to estimate lifetime cognitive change (P range 1.7e-04 to 0.038). After correction for multiple testing and adjustment for age and sex, no statistically significant associations were found between the SNPs and cognition. CRP is unlikely to be a causal determinant of late-life cognitive ability.

    Original languageEnglish
    Pages (from-to)3-11
    Number of pages9
    JournalBehavior Genetics
    Volume40
    Issue number1
    DOIs
    Publication statusPublished - Jan 2010

    Keywords

    • MENDELIAN RANDOMIZATION
    • ATHEROSCLEROSIS
    • DEMENTIA
    • FIBRINOGEN
    • DECLINE
    • Cognitive decline
    • METAANALYSIS
    • Cognition
    • INFLAMMATION
    • Inflammation
    • Single nucleotide polymorphism
    • MARKERS
    • DISEASE
    • ADULTS
    • C-reactive protein

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