Focus on single-gene effects limits discovery and interpretation of complex-trait-associated variants

Standard eQTL mapping and GWAS interpretation assume that each variant acts on one gene. However, neighboring genes can exhibit “allelic proxitropy,” where regulatory effects are shared. To identify these effects, we map QTLs on expression principal components of co-expressed neighboring genes. We discover QTLs and GWAS colocalizations missed by single-gene methods.