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, offspring's reading, and brain structure in a longitudinal neuroimaging study following 51 children from kindergarten through third grade. The results showed that greater PatAGE was significantly associated with worse reading, explaining an additional 9.5% of the variance 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 offspring's 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.

Highlights

  • There has been a global trend of postponed childbearing, especially in developed countries (Kohler, Billari, & Ortega, 2002)

  • ΔGMV significantly mediated the negative effect of advanced paternal age at childbirth (PatAGE) on offspring's reading; 95% confidence interval was [À0.406, À0.004] when nuisance variables, global measurements (TIV at t1, ΔTIV), and cognitive-linguistic precursors (t1PA, t1RAN) were statistically controlled. These results are in contrast to the commonly found results in the literature that we find in the present study, that is, t1PA mediates the negative effect of family history on offspring's reading (95% confidence interval was [À0.249, À0.001] when nuisance variables and the other cognitive-linguistic precursor (t1RAN) were controlled; Figure S2)

  • With the range of PatAGE restricted to 25– 47 years, we found PatAGE was negatively associated with reading performance measured using a variety of tests, even after controlling for strong predictors of reading that were not included in previous studies (Edwards & Roff, 2010; Saha et al, 2009)

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Summary

Introduction

There has been a global trend of postponed childbearing, especially in developed countries (Kohler, Billari, & Ortega, 2002). The pioneering study in 1978 reported a negatively skewed distribution of PatAGE in 48 boys with reading disorders (RD; a.k.a. and referred here to dyslexia) (Jayasekara & Street, 1978). Four decades later, this topic remains underinvestigated and the existing findings are controversial. When parental education and number of siblings were added to the statistical model, the effect of PatAGE on reading was no longer significant (Edwards & Roff, 2010). Such inconsistency underlines the importance of more research that controls for possible confounds in examining the PatAGE effect on reading

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