Abstract
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 = 4928). 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.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Molecular Psychiatry |
| Vol/bind | 30 |
| Udgave nummer | 8 |
| Sider (fra-til) | 3393-3403 |
| Antal sider | 11 |
| ISSN | 1359-4184 |
| DOI | |
| Status | Udgivet - 2025 |
Bibliografisk note
Funding Information: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). For the purpose of open access, we have applied a CC BY public copyright licence to any author-accepted manuscript version arising from this submission. S.B.-C. also received funding from the Autism Centre of Excellence, the Templeton World Charitable Fund, the MRC and the National Institute for Health Research Cambridge Biomedical Research Centre. The research was supported by the National Institute for Health Research Applied Research Collaboration East of England. Any views expressed are those of the author(s) and not necessarily those of the funder. Some of the results leading to this publication have received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement no. 777394 for the project AIMS-2-TRIALS. This joint undertaking receives support from the European Union\u2019s Horizon 2020 research and innovation program and the EFPIA and Autism Speaks, Autistica and the SFARI. The iPSYCH team was supported by grants from the Lundbeck Foundation (R102-A9118, R155-2014-1724 and R248-2017-2003), the NIMH (1R01MH124851-01 to A.D.B.), and EU\u2019s Horizon Europe program (R2D2-MH; grant agreement no. 101057385 to A.D.B.). The Danish National Biobank resource was supported by the Novo Nordisk Foundation. High-performance computer capacity for handling and statistical analysis of iPSYCH data on the GenomeDK HPC facility was provided by the Center for Genomics and Personalized Medicine and the Centre for Integrative Sequencing, iSEQ, Aarhus University, Denmark (grant to A.D.B.). Any views expressed are those of the author(s) and not necessarily those of the funders (IHI-JU2).
Publisher Copyright:
© The Author(s) 2025.