title: Childhood cognitive ability moderates later-life manifestation of type 2 diabetes genetic risk.
abstract: OBJECTIVE
  The study investigated whether childhood cognitive ability moderates Type 2 diabetes polygenic risk manifestation in older age.
  
  
  METHODS
  In 940 relatively healthy people (mean age 69.55 ± 0.85), we tested whether self-reported diabetes and hemoglobin HbA1c (HbA1c) levels were predicted by diabetes polygenic risk, cognitive ability measured about 60 years earlier, and their interaction. Polygenic risk scores aggregated the small effects of up to nearly 121,000 single-nucleotide polymorphisms (SNPs). Participants' cognitive ability was measured at age 11.
  
  
  RESULTS
  Both polygenic risk and low childhood cognitive ability significantly predicted diabetes diagnosis. Polygenic risk interacted with cognitive ability (p = .02), predicting HbA1c levels more strongly in people with below-median cognitive ability (effect r = .21) than in people with above-median cognitive ability (effect r = .10). The interaction term was not significant for self-reported diabetes (p = .34), although the genetic risk-diabetes association showed a tendency of being stronger among those with below-median cognitive ability.
  
  
  CONCLUSIONS
  Higher premorbid cognitive ability may provide some environmental protection against the manifestation of Type 2 diabetes genetic risk. This information may improve early identification of diabetes risk and inform intervention development.
authors.affiliation: University of Edinburgh.
authors.forename: René
authors.initials: R
authors.lastname: Mõttus
authors.affiliation: University of Edinburgh.
authors.forename: Michelle
authors.initials: M
authors.lastname: Luciano
authors.affiliation: University of Edinburgh.
authors.forename: John M
authors.initials: JM
authors.lastname: Sarr
authors.affiliation: University of Oxford.
authors.forename: Mark I
authors.initials: MI
authors.lastname: McCarthy
authors.affiliation: University of Edinburgh.
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Deary
mesh_terms: D000368:Aged; D003072:Cognition Disorders / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000473:pathology / Q000523:psychology; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors