Predicting cognitive ability in ageing cohorts using type 2 diabetes genetic risk

M. Luciano, R. Mõttus, S. E. Harris, G. Davies, A. Payton, W. E R Ollier, M. A. Horan, J. M. Starr, D. J. Porteous, N. Pendleton, I. J. Deary

    Research output: Contribution to journalArticlepeer-review


    Aims: To investigate whether there is overlap in the genetic determinants of Type 2 diabetes and cognitive ageing by testing whether a genetic risk score for Type 2 diabetes can predict variation in cognitive function in older people without dementia. Methods: Type 2 diabetes genetic risk scores were estimated using various single nucleotide polymorphism significance inclusion criteria from an initial genome-wide association study, the largest in Type 2 diabetes to date. Scores were available for 2775-3057 individuals, depending on the cognitive trait. Results: Type 2 diabetes genetic risk was associated with self-reported diabetes mellitus. Across varying single nucleotide polymorphism-inclusion levels, a significant association between Type 2 diabetes genetic risk and change in general cognitive function was found (median r = 0.04); however, this was such that higher Type 2 diabetes genetic risk related to higher cognitive scores. Conclusions: To investigate more fully the source of the often observed comorbidity between Type 2 diabetes and cognitive impairment, one direction for future research will be to use cognitive ability polygenic risk scores to predict Type 2 diabetes in line with the reverse causation hypothesis that people with lower pre-morbid cognitive ability are more likely to develop Type 2 diabetes. What's new?: The present study investigates whether the relationship between Type 2 diabetes mellitus and lower cognitive ability is attributable to genes predisposing to diabetes. Genes predisposing to diabetes (identified from the largest genome-wide association study of Type 2 diabetes to date) were not associated with lower cognitive abilities in older age. This suggests that any genetic basis for the association between diabetes and worsened cognition is attributable to those genes that are important for maintaining cognitive ability. Alternatively, environmental factors that influence diabetes risk and poorer cognition could explain this association. © 2013 The Authors.
    Original languageEnglish
    Pages (from-to)714-720
    Number of pages6
    JournalDiabetic Medicine
    Issue number6
    Early online date30 Jan 2014
    Publication statusPublished - Jun 2014


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