Genetic associations between fibrinogen and cognitive performance in three Scottish cohorts.
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.
Centre for Population Health Sciences, The University of Edinburgh, Medical School, Teviot Place, Edinburgh EH8 9AG, Scotland, UK. rem50@medschl.cam.ac.uk
Riccardo E
RE
Marioni
Ian J
IJ
Deary
Gordon D
GD
Murray
Gordon D O
GD
Lowe
Mark W J
MW
Strachan
Michelle
M
Luciano
Lorna M
LM
Houlihan
Alan J
AJ
Gow
Sarah E
SE
Harris
Ann
A
Rumley
Marlene C
MC
Stewart
F Gerry R
FG
Fowkes
Jackie F
JF
Price
D000368:Aged; D000375:Aging; D001241:Aspirin / Q000494:pharmacology; D050197:Atherosclerosis / Q000235:genetics; D003071:Cognition / Q000502:physiology*; D003072:Cognition Disorders / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D048909:Diabetes Complications / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D005260:Female; D005340:Fibrinogen / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012606:Scotland
D005340:Fibrinogen; D001241:Aspirin