Abstract
Brain regions communicate with each other through tracts of myelinated axons, commonly referred to as white matter. We identified common genetic variants influencing white matter microstructure using diffusion magnetic resonance imaging of 43,802 individuals. Genome-wide association analysis identified 109 associated loci, 30 of which were detected by tract-specific functional principal components analysis. A number of loci colocalized with brain diseases, such as glioma and stroke. Genetic correlations were observed between white matter microstructure and 57 complex traits and diseases. Common variants associated with white matter microstructure altered the function of regulatory elements in glial cells, particularly oligodendrocytes. This large-scale tract-specific study advances the understanding of the genetic architecture of white matter and its genetic links to a wide spectrum of clinical outcomes.