Autism spectrum disorder common variants associated with regional lobe volume variations at birth: cross-sectional study in 273 European term neonates in developing Human Connectome Project

Increasing lines of evidence suggest cerebral overgrowth in autism spectrum disorder (ASD) children in early life, but few studies have examined the effect of ASD common genetic variants on brain volumes in a general paediatric population. This study examined the association between ASD polygenic risk score (PRS) and volumes of the frontal, temporal, parietal, occipital, fronto-temporal and parieto-occipital lobes in 273 term-born infants of European ancestry in the developing Human Connectome Project. ASD PRS was positively associated with frontal (β = 0.027, pFDR = 0.04) and fronto-temporal (β = 0.024, pFDR = 0.01) volumes, but negatively with parietal (β = -0.037, pFDR = 0.04) and parieto-occipital (β = -0.033, pFDR = 0.01) volumes. This preliminary result suggests potential involvement of ASD common genetic variants in early structural variations linked to ASD. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Data were provided by the developing Human Connectome Project, KCL-Imperial-Oxford Consortium and the work was funded by ERC grant agreement no. 319456, the Wellcome EPSRC Centre for Medical Engineering at Kings College London (WT 203148/Z/16/Z) and by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guys and St Thomas NHS Foundation Trust and Kings College London. The views expressed are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. We are grateful to the families who generously supported this trial. HL is supported by the UK Medical Research Council (MR/N013700/1) and Kings College London member of the MRC Doctoral Training Partnership in Biomedical Sciences. HC is an academic clinical lecturer in Clinical Genetics at Kings College London and is supported by the NIHR. LCG received support from the Comunidad de Madrid-Spain Support for R&D Projects [BGP18/00178]. The authors acknowledge use of the research computing facility at Kings College London, Rosalind (https://rosalind.kcl.ac.uk). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics Approval Statement This study is based on a prospective sample of neonates participating in the dHCP (http://www.developingconnectome.org/). Data collection for the project took place in London, UK from 2015 to 2020. This project has received UK NHS research ethics committee approval (14/LO/1169, IRAS 138070), and written informed consent was obtained from parents. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data is available at https://biomedia.github.io/dHCP-release-notes/