title: Genetic variants associated with altered plasma levels of C-reactive protein are not associated with late-life cognitive ability in four Scottish samples.
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.
authors.affiliation: Public Health Sciences Section, Division of Community Health Sciences, Centre for Population Health Sciences, University of Edinburgh, Medical School, Teviot Place, EH8 9AG Edinburgh, Scotland, UK. R.E.Marioni@sms.ed.ac.uk
authors.forename: Riccardo E
authors.initials: RE
authors.lastname: Marioni
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Deary
authors.forename: Gordon D
authors.initials: GD
authors.lastname: Murray
authors.forename: Gordon D O
authors.initials: GD
authors.lastname: Lowe
authors.forename: Snorri B
authors.initials: SB
authors.lastname: Rafnsson
authors.forename: Mark W J
authors.initials: MW
authors.lastname: Strachan
authors.forename: Michelle
authors.initials: M
authors.lastname: Luciano
authors.forename: Lorna M
authors.initials: LM
authors.lastname: Houlihan
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Gow
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Harris
authors.forename: Marlene C
authors.initials: MC
authors.lastname: Stewart
authors.forename: Ann
authors.initials: A
authors.lastname: Rumley
authors.forename: F Gerry R
authors.initials: FG
authors.lastname: Fowkes
authors.forename: Jackie F
authors.initials: JF
authors.lastname: Price
mesh_terms: D000368:Aged; D000375:Aging; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000096:biosynthesis* / Q000235:genetics*; D003071:Cognition; D015331:Cohort Studies; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide; D012606:Scotland
chemical_list: D015415:Biomarkers; D002097:C-Reactive Protein