Mapping the association of polygenic risk scores with autism and ADHD traits in a single city region

The prevalence of autistic traits and Attention Deficit Hyperactivity Disorder (ADHD) traits is known to vary by location. The genetic and environmental aetiology of these traits may also vary spatially, with geographical environments amplifying or masking genetic influences. To investigate this, we constructed polygenic risk scores for autism and ADHD in participants from the Avon Longitudinal Study of Parents and Children (N=4,255 to 6,165). We estimated the association between polygenic risk and autistic and ADHD trait scores across the area surrounding the city of Bristol in the southwest of the United Kingdom. Mapping the results shows how associations between polygenic risk and trait scores varied by location. Our maps suggest that there is evidence of spatial variation in genetic associations for all traits. For social autistic traits and an autistic trait mean factor score, patterns of association were consistent among risk scores constructed at different p-value thresholds. The patterns for ADHD traits were more variable. We examined similarities between these maps and those of environmental variables associated with the prevalence of autism and ADHD, and found that in many cases the spatial distributions were correlated. This finding of spatial variation in genetic associations for autism and ADHD traits will help us better understand the factors that contribute to the complex interplay between the environment and genetic influence. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported in part by the UK Medical Research Council Integrative Epidemiology Unit at the University of Bristol (Grant ref: MC\_UU\_00011/1). The UK Medical Research Council and Wellcome Trust (Grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors and ZER and OSPD will serve as guarantors for the contents of this paper. A comprehensive list of grant funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). AB and RT were funded by the Natural Environment Research Council (Grant ref: R8/H12/83/NE/P01830/1) and the Medical Research Council (Grant ref: MC\_PC\_17210). ZER was supported by a Wellcome Trust PhD studentship (Grant ref: 109104/Z/15/Z). GWAS data for children were generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. OSPD is funded by the Alan Turing Institute under the EPSRC (Grant ref: EP/N510129/1). This study was also supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at the University Hospitals Bristol NHS Foundation Trust and the University of Bristol (BRC-1215-2011). ### 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: Ethical approval for the study was obtained from the ALSPAC Ethics and Law Committee and the Local Research Ethics Committees (University of Bristol) 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 and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data in the present study were obtained from ALSPAC after approval of our research proposal. Data can be requested by researchers as detailed on the ALSPAC website (http://www.bristol.ac.uk/alspac/researchers/access/).