Common genetic variation influencing human white matter microstructure

• Published in: Science (American Association for the Advancement of Science) Vol. 372; no. 6548
• Main Authors: Zhao, Bingxin, Li, Tengfei, Yang, Yue, Wang, Xifeng, Luo, Tianyou, Shan, Yue, Zhu, Ziliang, Xiong, Di, Hauberg, Mads E., Bendl, Jaroslav, Fullard, John F., Roussos, Panagiotis, Li, Yun, Stein, Jason L., Zhu, Hongtu
• Format: Journal Article
• Language: English
• Published: United States The American Association for the Advancement of Science 18.06.2021
• Subjects: Abnormalities; Anatomy; Anticonvulsants; Antidepressants; Antipsychotics; Association analysis; Attention deficit hyperactivity disorder; Axons; Brain; Brain - anatomy & histology; Brain - physiology; Brain architecture; Brain Diseases - genetics; Cardiovascular diseases; Clinical outcomes; Cognition; Cognitive ability; Dementia disorders; Diffusion; Diffusion Magnetic Resonance Imaging; Diffusion Tensor Imaging; Enrichment; Factor Analysis; Female; Gene regulation; Genetic abnormalities; Genetic diversity; Genetic variance; Genetic Variation; Genome, Human; Genome-wide association studies; Genome-Wide Association Study; Genomes; Genomics; Glioma; Health risks; Heart Disease Risk Factors; Heritability; Humans; In vivo methods and tests; Loci; Magnetic resonance imaging; Male; Medical imaging; Mental depression; Mental disorders; Mental Disorders - genetics; Microstructure; Movement disorders; Multifactorial Inheritance; Narcotics; Nervous system; Neural networks; Neural Pathways; Neurodegenerative diseases; Neuroglia - physiology; Neuroimaging; Neurological diseases; Neuronal-glial interactions; Neurons - physiology; Neurosciences; Oligodendrocytes; Parkinson's disease; Phenotypes; Population Distribution; Principal Component Analysis; Principal components analysis; Psychiatry; Quantitative Trait Loci; Risk analysis; Risk Factors; Schizophrenia; Standard error; Stroke; Substantia alba; Tensors; White Matter - diagnostic imaging; White Matter - physiology; White Matter - ultrastructure
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.abf3736

The white matter of the brain, which is composed of axonal tracts connecting different brain regions, plays key roles in both normal brain function and a variety of neurological disorders. Zhao et al. combined detailed magnetic resonance imaging–based assessment of brain structures with genetic data on nearly 44,000 individuals (see the Perspective by Filley). On the basis of this comprehensive analysis, the authors identified structural and genetic abnormalities associated with neurological and psychiatric disorders, as well as some nondisease traits, thus creating a valuable resource and providing some insights into the underlying neurobiology. Science , abf3736, this issue p. eabf3736 ; see also abj1881, p. 1265 A large-scale tract-specific study elucidates the genetic architecture of brain white matter and its links to a wide spectrum of clinical outcomes. 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.