title: Association between cognition and gene polymorphisms involved in thrombosis and haemostasis.
abstract: An association between blood markers of thrombosis and haemostasis and cognitive decline has been described. These results may be confounded by lifestyle and environmental factors. We used a Mendelian randomisation approach to describe the association between thrombosis/haemostasis genotypes and cognition. We studied the genetic variants (single nucleotide polymorphisms) of circulating markers of thrombosis and haemostasis. Our chosen blood factors and associated polymorphisms were D-dimer [rs12029080], fibrinogen [rs1800789], plasminogen activator inhibitor [rs2227631], and von Willebrand factor [rs1063857]. We described association with multidomain cognitive test scores using data from the Scottish Family Health Study. Cognitive data were analysed for individual tests and combined to give a general cognitive factor. In 20,288 subjects, we found no evidence of association between cognitive function (individual tests and combined scores) and any of the above-mentioned single nucleotide polymorphisms. Lower scores on cognitive measures were associated with increasing age, socioeconomic deprivation, blood pressure, waist-hip ratio, smoking, and vascular comorbidity (all p < 0.001). In a post hoc sensitivity analysis restricted to those aged over 50 years, there was still no signal of association. Our data add to our understanding of determinants of cognition but are not definitive; the variation in blood levels explained by SNPs was modest and our sample size may have been insufficient to detect a modest association.
authors.affiliation: Institute of Cardiovascular and Medical Sciences, University of Glasgow, New Lister Building, Glasgow Royal Infirmary, Glasgow, G31 2ER, UK, terry.quinn@glasgow.ac.uk.
authors.forename: Terence J
authors.initials: TJ
authors.lastname: Quinn
authors.forename: Jahad
authors.initials: J
authors.lastname: Alghamdi
authors.forename: Sandosh
authors.initials: S
authors.lastname: Padmanabhan
authors.forename: David J
authors.initials: DJ
authors.lastname: Porteous
authors.forename: Blair H
authors.initials: BH
authors.lastname: Smith
authors.forename: Lynne
authors.initials: L
authors.lastname: Hocking
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Deary
authors.forename: John
authors.initials: J
authors.lastname: Gallacher
authors.forename: Martina
authors.initials: M
authors.lastname: Messow
authors.forename: David J
authors.initials: DJ
authors.lastname: Stott
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003072:Cognition Disorders / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000235:genetics*; D006487:Hemostasis / Q000235:genetics; D006801:Humans; D057187:Independent Living; D008297:Male; D057182:Mendelian Randomization Analysis; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012606:Scotland; D013927:Thrombosis / Q000235:genetics* / Q000523:psychology; D055815:Young Adult; D014841:von Willebrand Factor / Q000235:genetics*
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; D017395:Plasminogen Activator Inhibitor 1; C036309:fibrin fragment D; D014841:von Willebrand Factor