Abstract
OBJECTIVE: The study investigated whether childhood cognitive ability moderates Type 2 diabetes polygenic risk manifestation in older age. METHOD: 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.