AbstractExpression quantitative trait loci (eQTL) are genetic variants associated with gene expression. Using genome-wide genotype data, it is now possible to impute gene expression using eQTL mapping efforts. This approach can be used to analyse previously unexplored relationships between gene expression and heritable in vivo measures of human brain structural connectivity. Using large-scale eQTL mapping studies, we computed 6457 gene expression scores (eQTL scores) using genome-wide genotype data in UK Biobank, where each score represents a genetic proxy measure of gene expression. These scores were then tested for associations with two diffusion tensor imaging measures, fractional anisotropy (N_FA = 14,518) and mean diffusivity (N_MD = 14,485), representing white matter structural integrity. We found FDR-corrected significant associations between 8 eQTL scores and structural connectivity phenotypes, including global and regional measures (β_absolute FA = 0.0339–0.0453; MD = 0.0308–0.0381) and individual tracts (β_absolute FA = 0.0320–0.0561; MD = 0.0295–0.0480). The loci within these eQTL scores have been reported to regulate expression of genes involved in various brain-related processes and disorders, such as neurite outgrowth and Parkinson’s disease (DCAKD, SLC35A4, SEC14L4, SRA1, NMT1, CPNE1, PLEKHM1, UBE3C). Our findings indicate that eQTL scores are associated with measures of in vivo brain connectivity and provide novel information not previously found by conventional genome-wide association studies. Although the role of expression of these genes regarding white matter microstructural integrity is not yet clear, these results suggest it may be possible, in future, to map potential trait- and disease-associated eQTL to in vivo brain connectivity and better understand the mechanisms of psychiatric disorders and brain traits, and their associated imaging findings.