Genetic risk for insulin resistance and cognitive scores
Our findings suggest that a higher genetic risk for insulin resistance in children was associated with lower cognitive scores in both Asian and European cohorts.
Studies have shown that dysfunctional insulin signalling can worsen pathology related to Alzheimer’s disease, suggesting insulin resistance is a link between metabolic syndrome and neurodegenerative disorders. The relationships of early-life insulin resistance or fasting glucose concentration with cognitive function are less studied.
We constructed PRS for child glycaemic traits using child, maternal, and paternal genotypes in an Asian parent-offspring cohort (GUSTO) and found that child PRS and parental PRS were differently associated with cognitive function. Most consistently, we found that a higher child polygenic risk for HOMA-IR was associated with lower scores for perceptual reasoning (WASI-II) and academic performance (WIAT-III mean score). A higher paternal polygenic risk for child HOMA-IR was also found to be associated with a lower score for perceptual reasoning in the GUSTO cohort.
Replication analysis in a European birth cohort (ALSPAC) showed that higher maternal PRS for HOMA-IR was associated with a lower performance IQ score in girls. This may suggest different roles of parental genomes and that the relationship between polygenic risk for glycaemic regulation and neurodevelopment may be specific to neurodevelopmental domains and populations. Such differences in different populations suggest further research is warranted on whether these associations are robust to different environments.
In summary, for the first time, our findings suggest that a higher genetic risk for insulin resistance in children was associated with lower cognitive scores in both Asian and European cohorts. Some differential findings between cohorts may be attributed to genetic and environmental factors. Our findings suggest that monitoring and early intervention of insulin resistance should be considered for child development to enhance human capital.
For more details, see Huang J, et al. Parental and child genetic burden of glycaemic dysregulation and early-life cognitive development: an Asian and European prospective cohort study. Translational Psychiatry. 2024.