Analyzing direct and indirect genetic effects on early neurodevelopmental traits - a commentary on Hegemann et al

The study by Hegemann et al. advances understanding of the genetic architecture underlying early neurodevelopmental traits by distinguishing direct and indirect genetic effects using Trio-GCTA and polygenic score models. Findings reveal that indirect genetic effects are particularly pronounced for hyperactivity and restricted and repetitive behaviors, while direct effects dominate in language and motor development. Notably, associations between parental cognitive and educational attainment polygenic scores and child outcomes suggest potential protective genetic influences. However, several methodological considerations may affect interpretation. Excluding closely related individuals could limit the detection of extended familial effects, and reliance on polygenic scores derived from predominantly European GWAS may constrain generalizability. Furthermore, current PGS explain only a portion of trait heritability, possibly underrepresenting true genetic contributions. Future studies incorporating extended family structures, diverse populations, and alternative methods to model gene-environment interplay are essential for refining insights into early neurodevelopmental processes.