Genetic Variants Associated With Altered Plasma Levels of C-Reactive Protein are not Associated With Late-Life Cognitive Ability in Four Scottish Samples
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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.
KeywordsC-reactive protein Inflammation Cognition Cognitive decline Single nucleotide polymorphism
We thank participants and staff of all the studies, including staff at the Wellcome Trust Clinical Research Facility in Edinburgh where research clinics were held. The AAA Trial was supported by the Wellcome Trust, Chest Heart and Stroke Scotland, the British Heart Foundation and the Chief Scientist Office, Scotland. LBC1936 data collection was supported by a programme grant from Research into Ageing and continues as the Disconnected Mind project funded by Help the Aged. Data collection in the baseline ET2DS was funded by the Medical Research Council, which also funds REM. IJD, ML, LMH, AJG, SHE, and JFP are members of the University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology. The Centre is part of the cross council Lifelong Health and Wellbeing Initiative. Funding from the BBSRC, EPSRC, ESRC and MRC is gratefully acknowledged.
Conflict of interest statement
There are no conflicts of interest for any of the authors.
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