Polygenic Scores for Autism Are Associated with Reduced Neurite Density in Adults and Children from the General Population

Overview

Journal Mol Psychiatry

Specialties Molecular Biology
Psychiatry

Date 2025 Feb 24

PMID 39994426

Authors

Yuanjun Gu

Eva Maria-Stauffer

Saashi A Bedford

Rafael Romero-Garcia

Jakob Grove

Anders D Borglum

Hilary Martin

Simon Baron-Cohen

Richard A I Bethlehem

Varun Warrier

Affiliations

Soon will be listed here.

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.

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