Development of thalamus mediates paternal age effect on offspring reading: A preliminary investigation

Abstract

The importance of (inherited) genetic impact in reading development is well-established. De novo mutation is another important contributor that is recently gathering interest as a major liability of neurodevelopmental disorders, but has been neglected in reading research to date. Paternal age at childbirth (PatAGE) is known as the most prominent risk factor for de novo mutation, which has been repeatedly shown by molecular genetic studies. As one of the first efforts, we performed a preliminary investigation of the relationship between PatAGE, offsprings reading, and brain structure in a longitudinal neuroimaging study following 51 children from kindergarten through third grade. The results showed that greater PatAGE was associated significantly with worse reading, explaining an additional 9.5% of the variations after controlling for a number of confounds--including familial factors and cognitive-linguistic reading precursors. Moreover, this effect was mediated by volumetric maturation of the left posterior thalamus from ages 5 to 8. Complementary analyses indicated the PatAGE-related thalamic region was most likely located in the pulvinar nuclei and related to the dorsal attention network by using brain atlases, public datasets, and offsprings diffusion imaging data. Altogether, these findings provide novel insights into neurocognitive mechanisms underlying the PatAGE effect on reading acquisition during its earliest phase and suggest promising areas of future research. HighlightsO_LIPaternal age at childbirth (PatAGE) is negatively correlated with offsprings reading abilities. C_LIO_LIPatAGE is related to volumetric maturation of the left posterior thalamus. C_LIO_LIThalamic development mediates the PatAGE effect on reading. C_LIO_LIThe PatAGE-related thalamic area is more likely to connect with the dorsal attention network. C_LI