An early grasp of language can shape a child’s life. Toddlers with stronger language abilities tend to perform better in school, have sharper cognitive functions, and even be at reduced risk of psychosocial disabilities and Alzheimer’s disease in later years.
A key biological driver behind language development is brain myelination: the insulation of nerve fibres with lipid-rich sheaths that help signals travel efficiently. While various genetic and lifestyle factors seem to affect myelination, researchers have noted links between childhood obesity and poorer neurocognitive functions, including language abilities.
But is obesity a cause, or a sign? “Both childhood obesity and language development are shaped by early-life social conditions,” said Jian Huang, a Senior Scientist at A*STAR Institute for Human Development and Potential (A*STAR IHDP). “These shared factors make it hard to disentangle whether the associations are due to obesity itself, or to the environment in which both obesity and language development arise.”
To cut through the noise, a multi-institutional team including Huang and A*STAR IHDP colleagues investigated how genetically predicted obesity might shape speech and language skills in growing children. The team comprised researchers from the A*STAR Bioinformatics Institute (A*STAR BII); the National University of Singapore, KK Women’s and Children’s Hospital, the National University Hospital, and Duke-NUS Medical School in Singapore; as well as institutes from the UK and Canada.
The Growing up in Singapore Towards Healthy Outcomes (GUSTO) cohort study team collected a wide range of data and biological samples from about 1,000 children during different developmental stages. In this study, the research team leveraged the genetic, proteomic, brain imaging and language development data to investigate the connection between obesity related genetics and language development. To calculate polygenic risk scores (PRS) for obesity—an estimate of genetic predisposition towards a higher body mass index (BMI)—they used a trans-ancestry approach. This approach takes advantage of genome-wide association studies (GWAS) from both European and Asian populations in order to improve the accuracy of risk scoring in the multi-ethnic GUSTO cohort.
A series of genetic analyses found that while GUSTO children with higher obesity PRS, particularly boys, scored lower on language tests at ages four and nine. Using Mendelian randomisation—a method for testing causality with genetics—they suggested that obesity itself was unlikely to cause weaker linguistic skills. Instead, the two traits appeared to share genetic roots.
To examine the underlying molecular mechanisms, the researchers examined blood levels of 92 neurology-related proteins alongside language-related MRI-based brain microstructure. One protein, ephrin-A4 (EFNA4), stood out: higher levels of EFNA4 were tied to higher obesity PRS. EFNA4 expression was also associated with language ability and fractional anisotropy of language-related white matter tracts, suggesting a role in brain myelination. The expression of the EPH-ephrin molecular pathway, which involves EFNA4, was also associated with lower language scores in boys.
“This suggests that metabolic and neurodevelopmental health are intertwined at the biological level,” said Huang. “There are shared genomic pathways that influence both obesity risk and language development through processes such as the EPH-Ephrin signalling pathway, which regulates brain myelination.”
The A*STAR-affiliated researchers contributing to this research are from the A*STAR Institute for Human Development and Potential (A*STAR IHDP) and A*STAR Bioinformatics Institute (A*STAR BII).
