| Title: | Polygenic scores for autism are associated with reduced neurite density in adults and children from the general population |
| Journal: | Molecular Psychiatry |
| Published: | 24 Feb 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/39994426/ |
| DOI: | https://doi.org/10.1038/s41380-025-02927-z |
| URL: | https://kclpure.kcl.ac.uk/portal/en/publications/e4404cd2-95b5-45b1-94a2-4a5051917b41 |
Publication 15896
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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.</p>
19 Keywords
- Adult
- Autism Spectrum Disorder
- Autistic Disorder
- Brain
- Cerebral Cortex
- Child
- Female
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Humans
- Magnetic Resonance Imaging
- Male
- Mendelian Randomization Analysis
- Middle Aged
- Multifactorial Inheritance
- Neurites
- Polymorphism, Single Nucleotide
- United Kingdom
- White Matter
10 Authors
- Yuanjun Gu
- Eva Maria-Stauffer
- Saashi A. Bedford
- Rafael Romero-Garcia
- Jakob Grove
- Anders D. Børglum
- Hilary Martin
- Simon Baron-Cohen
- Richard A. I. Bethlehem
- Varun Warrier
1 Application
| Application ID | Title |
|---|---|
| 20904 | Genetic and phenotypic investigation of neural brain network connectivity |
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