Polygenic scores for autism are associated with  reduced neurite density in adults and children  from the general population

Gu, Yuanjun; Maria-Stauffer, Eva; Bedford, Saashi; Romero-Garcia, Rafael; Grove, Jakob; Børglum, Anders; Martin, Hilary; Baron-Cohen, Simon; Bethlehem, Richard; Warrier, Varun

Polygenic scores for autism are associated with reduced neurite density in adults and children from the general population

Authors

Gu, Yuanjun

Maria-Stauffer, Eva

Bedford, Saashi

Romero-Garcia, Rafael

Publisher

Springer Nature [academic journals on nature.com]
Department of Psychiatry Student
https://doi.org/10.1038/s41380-025-02927-z

Description

Genetic variants linked to autism are thought to change cognition and behaviour by altering the structure and function of the brain. Although a substantial body of literature has identified structural brain differences in autism, it is unknown whether autism-associated common genetic variants are linked to changes in cortical macro- and micro-structure. We investigated this using neuroimaging and genetic data from adults (UK Biobank, N = 31,748) and children (ABCD, N = 4,928). Using polygenic scores and genetic correlations we observe a robust negative association between common variants for autism and a magnetic resonance imaging derived phenotype for neurite density (intracellular volume fraction) in the general population. This result is consistent across both children and adults, in both the cortex and in white matter tracts, and confirmed using polygenic scores and genetic correlations. There were no sex differences in this association. Mendelian randomisation analyses provide no evidence for a causal relationship between autism and intracellular volume fraction, although this should be revisited using better powered instruments. Overall, this study provides evidence for shared common variant genetics between autism and cortical neurite density.
This research was supported by funding from the Simons Foundation for Autism Research Initiative, the Wellcome Trust (214322\Z\18\Z), Horizon-Europe R2D2-MH (grant agreement number 101057385), and UKRI (10063472).