Genetic Associations Between Fibrinogen and Cognitive Performance in Three Scottish Cohorts
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There is increasing evidence to suggest that elevated plasma levels of fibrinogen are associated with late-life cognitive performance. This study tested the association of single nucleotide polymorphisms in the fibrinogen α (FGA) and β (FGB) genes with cognitive performance. Data were analysed from three community-dwelling populations of older persons (>50 years) in central Scotland: the Aspirin for Asymptomatic Atherosclerosis (AAA) Trial (n = 2,091), the Edinburgh Type 2 Diabetes Study (ET2DS, n = 1,066), and the Lothian Birth Cohort 1936 (LBC1936, n = 1,091). Cognition was assessed using a battery of five, seven, and four psychometric tests, respectively. This information was used to derive a general cognitive factor. Weakly significant associations were found between the rs4220 (FGB), and rs2227412 (FGB) SNPs and a single test of cognitive performance in the AAA Trial (p < 0.05). These findings did not replicate in the LBC1936 or ET2DS cohorts, except for the rs2227412 SNP, which was significantly associated with the general cognitive factor in the ET2DS (p = 3.3 × 10−4). A summary term that combined results from all three studies suggested that the rs2227412 genotype associated with reduced cognitive ability also associated with higher plasma fibrinogen levels. These findings suggest a tentative role for fibrinogen as a determinant of late-life cognitive performance and justify further attempts at replication in older persons.
KeywordsAgeing Fibrinogen Cognition Single nucleotide polymorphism Diabetes
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 funded REM. IJD, ML, LMH, AJG, SEH, and JFP are members of the University of Edinburgh Centre for Cognitive Aging and Cognitive Epidemiology. The Centre is part of the cross council Lifelong Health and Wellbeing Initiative (G0700704/84698). Funding from the BBSRC, EPSRC, ESRC and MRC is gratefully acknowledged.
Conflicts of interest
There are no conflicts of interest for any of the authors.
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