Brain regions communicate with each other via tracts of myelinated axons, commonly referred to as white matter. White matter microstructure can be measured in the living human brain using diffusion based magnetic resonance imaging (dMRI), and has been found to be altered in patients with neuropsychiatric disorders. Although under strong genetic control, few genetic variants influencing white matter microstructure have ever been identified. Here we identified common genetic variants influencing white matter microstructure using dMRI in 42,919 individuals (35,741 in the UK Biobank). The dMRIs were summarized into 215 white matter microstructure traits, including 105 measures from tract-specific functional principal component analysis. Genome-wide association analysis identified many novel white matter microstructure associated loci (P < 2.3 * 10^{-10}). We identified shared genetic influences through genetic correlations between white matter tracts and 62 other complex traits, including stroke, neuropsychiatric disorders (e.g., ADHD, bipolar disorder, major depressive disorder, schizophrenia), cognition, neuroticism, chronotype, as well as non-brain traits. Common variants associated with white matter microstructure alter the function of regulatory elements in glial cells, particularly oligodendrocytes. White matter associated genes were enriched in pathways involved in brain disease pathogenesis, neurodevelopment process, and repair of white matter damage (P < 1.5 * 10^{-8}). In summary, this large-scale tract-specific study provides a big step forward in understanding the genetic architecture of white matter and its genetic links to a wide spectrum of clinical outcomes.

中文翻译：

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影响人类白质微观结构的常见遗传变异

脑区通过有髓的轴突（通常称为白质）束相互交流。可以使用基于扩散的磁共振成像（dMRI）在活的人脑中测量白​​质的微结构，并且发现神经精神疾病患者的白质微结构会发生变化。尽管在强大的遗传控制下，几乎没有发现影响白质微观结构的遗传变异。在这里，我们使用dMRI在42,919个人（英国生物银行中的35,741）中确定了影响白质微结构的常见遗传变异。dMRIs被归纳为215种白质显微结构特征，其中包括105种来自区域特异性功能主成分分析的量度。全基因组关联分析确定了许多新颖的白质微观结构相关基因座（P <2。3 * 10 ^ {-10}）。我们通过白质束与62个其他复杂性状之间的遗传相关性，确定了共享的遗传影响，这些中性状包括中风，神经精神疾病（例如，多动症，双相情感障碍，重性抑郁症，精神分裂症），认知，神经质，表型以及非脑性特质。与白质微结构相关的常见变体会改变神经胶质细胞（尤其是少突胶质细胞）中调控元件的功能。白质相关基因丰富于脑疾病发病机制，神经发育过程和白质损伤修复的通路（P <1.5 * 10 ^ {-8}）。总而言之，这项大规模的针对特定领域的研究为理解白质的遗传结构及其与广泛的临床结果之间的遗传联系，迈出了一大步。我们通过白质束与62个其他复杂性状之间的遗传相关性，确定了共享的遗传影响，这些中性状包括中风，神经精神疾病（例如，多动症，双相情感障碍，重性抑郁症，精神分裂症），认知，神经质，表型以及非脑性特质。与白质微结构相关的常见变体会改变神经胶质细胞（尤其是少突胶质细胞）中调控元件的功能。白质相关基因丰富于脑疾病发病机制，神经发育过程和白质损伤修复的通路（P <1.5 * 10 ^ {-8}）。总而言之，这项大规模的针对特定领域的研究为理解白质的遗传结构及其与广泛的临床结果之间的遗传联系，迈出了一大步。我们通过白质束与62个其他复杂性状之间的遗传相关性，确定了共享的遗传影响，这些中性状包括中风，神经精神疾病（例如，多动症，双相情感障碍，重性抑郁症，精神分裂症），认知，神经质，表型以及非脑性特质。与白质微结构相关的常见变体会改变神经胶质细胞（尤其是少突胶质细胞）中调控元件的功能。白质相关基因丰富于脑疾病发病机制，神经发育过程和白质损伤修复的通路（P <1.5 * 10 ^ {-8}）。总而言之，这项大规模的针对特定领域的研究为理解白质的遗传结构及其与广泛的临床结果之间的遗传联系，迈出了一大步。