24. POLYGENIC SCORES FOR AUTISM ARE ASSOCIATED WITH NEURITE DENSITY IN ADULTS AND CHILDREN FROM THE GENERAL POPULATION

Abstract:

Background 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. Methods In the study, we used neuroimaging and genetic data from adults (UK Biobank, N = 31,748) and children (ABCD, N = 4,928). Fixed-effect linear regression models under 9 different hypotheses were used to systematically explore the associations between PGS for autism and global and regional magnetic resonance imaging (MRI)-derived cortical phenotypes, modified by age and biological sex. We then followed up the results with genetic correlation analysis, functional network enrichment analysis, and two-way mendelian randomisation, to attempt to further understand the meaning of the associations observed. Results 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. Discussion Overall, this study provides evidence for shared common variant genetics between autism and cortical neurite density. Disclosure Nothing to disclose.