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

Abstract

AbstractThe 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.