Autism common variants associated with white matter alterations at birth: cross-sectional fixel-based analyses of 221 European term-born neonates from the developing human connectome project

Hai Le; Alexandra F Bonthrone; Alena Uus; Daphna Fenchel; Alexandra Lautarescu; Konstantina Dimitrakopoulou; A David Edwards; Joseph V Hajnal; Serena J Counsell; Lucilio Cordero-Grande; Daan Christiaens; Dafnis Batalle; Maximilian Pietsch; Anthony N Price; Hamel Patel; Charles Curtis; Harriet Cullen; Maria Deprez; Jacques-Donald Tournier

doi:10.1038/s41398-025-03252-3

Autism common variants associated with white matter alterations at birth: cross-sectional fixel-based analyses of 221 European term-born neonates from the developing human connectome project

Transl Psychiatry. 2025 Feb 4;15(1):40. doi: 10.1038/s41398-025-03252-3.

Authors

Hai Le¹, Alexandra F Bonthrone², Alena Uus², Daphna Fenchel², Alexandra Lautarescu^{2

3}, Konstantina Dimitrakopoulou⁴, A David Edwards², Joseph V Hajnal², Serena J Counsell², Lucilio Cordero-Grande^{2

5}, Daan Christiaens², Dafnis Batalle^{2

3}, Maximilian Pietsch², Anthony N Price², Hamel Patel⁶, Charles Curtis^{6

7}, Harriet Cullen^#^{2

8}, Maria Deprez^#², Jacques-Donald Tournier^#²

Affiliations

¹ Research Department of Early Life Imaging, School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK. L.haibg@gmail.com.
² Research Department of Early Life Imaging, School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK.
³ Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
⁴ Translational Bioinformatics Platform, NIHR Biomedical Research Centre, Guy's and St. Thomas' NHS Foundation Trust and King's College London, London, UK.
⁵ Biomedical Image Technologies, ETSI Telecomunicación, Universidad Politécnica de Madrid & CIBER-BBN, ISCIII, Madrid, Spain.
⁶ NIHR BioResource Centre Maudsley, NIHR Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust & Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
⁷ Social Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
⁸ Department of Medical and Molecular Genetics, School of Basic and Medical Biosciences, King's College London, London, UK.

^# Contributed equally.

Abstract

Increasing lines of evidence suggest white matter (WM) structural changes associated with autism can be detected in the first year of life. Despite the condition having high heritability, the relationship between autism common genetic variants and WM changes during this period remains unclear. By employing advanced regional and whole-brain fixel-based analysis, the current study investigated the association between autism polygenic scores (PS) and WM microscopic fibre density and macrostructural morphology in 221 term-born infants of European ancestry from the developing Human Connectome Project. The results suggest greater tract mean fibre-bundle cross-section of the left superior corona radiata is associated with higher autism PS. Subsequent exploratory enrichment analysis revealed that the autism risk single nucleotide polymorphisms most associated with the imaging phenotype may have roles in neuronal cellular components. Together, these findings suggest a possible link between autism common variants and early WM development.

MeSH terms

Autistic Disorder* / diagnostic imaging
Autistic Disorder* / genetics
Autistic Disorder* / pathology
Brain* / diagnostic imaging
Brain* / pathology
Connectome
Cross-Sectional Studies
Female
Humans
Infant, Newborn
Magnetic Resonance Imaging
Male
Multifactorial Inheritance
Polymorphism, Single Nucleotide
White Matter* / diagnostic imaging
White Matter* / growth & development
White Matter* / pathology
White People / genetics

Abstract

MeSH terms

Grants and funding