Developing and sharing polygenic risk scores for 4,206 brain imaging-derived phenotypes for 400,000 UK Biobank subjects not participating in the imaging study

The UK Biobank’s brain imaging data is an essential resource for clinical research, but its cost and difficulty in obtaining limit the imaging study to only 100,000 participants, leaving the majority of UKB subjects without imaging data. However, because imaging-derived phenotypes (IDPs) are heritable, and most UKB subjects have genetic information available, it’s possible to predict IDPs for UKB subjects outside the imaging study using genetic data. To this end, this study systematically developed and evaluated biobank-scale genetic polygenic risk scores (PRS) for 4,206 IDPs from multiple brain imaging modalities and processing pipelines. The results indicate that the majority of IDPs (64.76%, 2,774/4,206) were significantly predicted by PRS developed by subjects with both genetic and imaging data. Moreover, genetically predicted IDPs showed associations with a wide range of complex traits and diseases, with the patterns being consistent across different imaging pipelines. These findings suggest that genetic prediction through PRS is a cost-effective and practical way to make the UKB imaging study more beneficial to a broader population. The PRS data resources developed in this study have been made publicly available through Zenodo and will be returned to the UK Biobank. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The study has been partially supported by funding from the Wharton Dean's Research Fund and Analytics at Wharton, as well as start-up funds from Purdue Statistics Department. ### 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: The individual-level data used in the present study have been openly available from the UK Biobank (https://www.ukbiobank.ac.uk/) study. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the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 PRS data resources have been made publicly available at Zenodo (https://doi.org/10.5281/zenodo.7709788). The individual-level data used in this study can be obtained from https://www.ukbiobank.ac.uk/.