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.

大脑区域通过大量有髓轴突（通常称为白质）相互交流。我们使用 43,802 个人的扩散磁共振成像确定了影响白质微结构的常见遗传变异。全基因组关联分析确定了 109 个相关位点，其中 30 个通过特定区域的功能主成分分析检测到。许多与脑部疾病共定位的基因座，例如神经胶质瘤和中风。观察到白质微结构与 57 种复杂性状和疾病之间存在遗传相关性。与白质微结构相关的常见变体改变了神经胶质细胞中调节元件的功能，特别是少突胶质细胞。