Investigation of metabolomic biomarkers for childhood executive function and the role of genetic and dietary factors: The GUSTO cohort

Investigation of metabolomic biomarkers for childhood executive function and the role of genetic and dietary factors: The GUSTO cohort

eBioMedicine

10.1016/j.ebiom.2022.104111

http://dx.doi.org/10.1016/j.ebiom.2022.104111

Jian Huang, Evelyn Law, Ibrahim Karaman, Keri McCrickerd, Anna Fogel, Mary F.F. Chong, Lourdes Mary Daniel, Patricia Pelufo Silveira, Yap Seng Chong, Johan G. Eriksson, Michael J. Meaney, Jonathan Huang

General Biochemistry, Genetics and Molecular Biology, General Medicine

18 June 2022

Huang, J., Law, E., Karaman, I., McCrickerd, K., Fogel, A., Chong, M. F. F., Daniel, L. M., Silveira, P. P., Chong, Y. S., Eriksson, J. G., Meaney, M. J., & Huang, J. (2022). Investigation of metabolomic biomarkers for childhood executive function and the role of genetic and dietary factors: The GUSTO cohort. EBioMedicine, 81, 104111. https://doi.org/10.1016/j.ebiom.2022.104111

Background Few studies have investigated molecular biomarkers of specific executive function (EF) skills in children. We aimed to characterise the prospective associations between metabolome and multiple domains of EF using a bidirectional design. Methods This study was conducted within a longitudinal birth cohort, the Growing Up in Singapore Towards healthy Outcomes (GUSTO). Circulating levels of 165 metabolites were quantified using a nuclear magnetic resonance based metabolomics platform (n = 457 (∼6yrs) and n = 524 (∼8yrs)). Parent-reported EF was available for 495 children (∼7yrs). Multivariate linear regression was used to assess the metabolite-EF relationships. We examined the role of body composition, dietary factors, and genetics in the metabolite-EF associations. Findings Higher leucine level (∼6yrs) was associated with poorer EF (∼7yrs, Initiate (P = 0.003) and Working Memory (P = 0.004)). EF (∼7yrs) was not associated with leucine (∼8yrs). Importantly, we found weak evidence for associations of dietary factors (∼5yrs) with leucine (∼6yrs) and EF (∼7yrs). Each copy of C allele in rs1260326 (a leucine-related polymorphism) was associated with higher leucine level and poorer Initiate and Working Memory (P < 0.05). Amongst those with less strongly genetically influenced leucine, inverse association between leucine and cognitive regulation were weaker among those with higher BMI. Interpretation The observed association between higher leucine level and poorer EF may be determined by genetics and may not be easily amenable to dietary interventions. Further research is needed for validation and to understand mechanisms. Funding Singapore National Research Foundation and Agency for Science, Technology and Research.

Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)

This research / project is supported by the Ministry of Health’s (MOH)/ National Medical Research Council (NMRC) - Open Fund-Large Collaborative Grant
Grant Reference no. : OF-LCG; MOH-000504

This research / project is supported by the National Research Foundation (NRF) - Human Potential Programme
Grant Reference no. : NA

https://oar.a-star.edu.sg/communities-collections/articles/19102

2352-3964

Singapore Institute for Clinical Sciences