An expanded set of genome-wide association studies of brain imaging phenotypes in UK Biobank

UK Biobank is a major prospective epidemiological study, including multimodal brain imaging, genetics and ongoing health outcomes. Previously, we published genome-wide associations of 3,144 brain imaging-derived phenotypes, with a discovery sample of 8,428 individuals. Here we present a new open resource of genome-wide association study summary statistics, using the 2020 data release, almost tripling the discovery sample size. We now include the X chromosome and new classes of imaging-derived phenotypes (subcortical volumes and tissue contrast). Previously, we found 148 replicated clusters of associations between genetic variants and imaging phenotypes; in this study, we found 692, including 12 on the X chromosome. We describe some of the newly found associations, focusing on the X chromosome and autosomal associations involving the new classes of imaging-derived phenotypes. Our novel associations implicate, for example, pathways involved in the rare X-linked STAR (syndactyly, telecanthus and anogenital and renal malformations) syndrome, Alzheimer's disease and mitochondrial disorders. The Elliott and Smith teams used imaging and genetics data from 40,000 volunteers in the UK Biobank healthcare study, discovering new genetic influences over brain structure and function, which are of relevance to both rare and common diseases.

Automated summary

This study utilized data from the UK Biobank to identify 692 clusters of associations between genetic variants and imaging phenotypes, including 12 on the X chromosome, revealing pathways related to rare diseases such as the STAR syndrome, Alzheimer's disease, and mitochondrial disorders.