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.

The authors have declared no competing interest.

This study was funded by the Simons Foundation; Wellcome Trust (Wellcome), ref number 214322\Z\18\Z; EU Framework Programme for Research and Innovation H2020, ref number 101057385; and UK Research and Innovation , Grant Reference Number 10063472

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This study is based on data from two independent cohorts, the UK Biobank (UKB) and the Adolescent Brain Cognitive Development (ABCD) database. Ethical approval was obtained from the Human Biology Research Ethics Committee, University of Cambridge (Cambridge, UK). Informed consent was provided by all participants.

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All raw code and data produced are available online at https://github.com/yg330/autism.img-pgs. GWAS summary statistics and cortical morphology data are available through request from the CAM:IDE Data Access Portal (https://portal.ide-cam.org.uk/overview/483). iPSYCH-based GWAS data for autism [49] can be requested from Jakob Grove and Anders Borglum.

https://github.com/ucam-department-of-psychiatry/maps_and_parcs