Recently, a genome-wide association study has identified genetic variants that influence white matter microstructure in the brain.
White matter was once believed to be passive tissue in the brain. However, it is now understood that white matter is crucial for overall brain function, in particular cognitive learning. Also, damage to white matter has now been linked to a variety of neurological disorders, such as strokes and dementia.
White matter is found in deep subcortical tissues of the brain and is composed of axonal tracts. These bundles of nerve fibres connect all four lobes of the brain, and the limbic system, together. White matter provides this connectivity by organising the distribution of neural networks, which are widely scattered neurons that fire in synchrony.
Although it is recognised that white matter differences between individuals could be heritable, few common genetic variants that influence white matter microstructure have been identified, until now.
Image credit: Frontiers for Young Minds: White Matter Counts
Genetic variants influence white matter
Recently, researchers conducted a genome-wide association study (GWAS), using diffusion magnetic resonance imaging (dMRI), to identify genetic factors that affect white matter microstructure. Twenty-one cerebral white matter tracts were analysed in over 43,000 individuals. Also, dMRI enabled the study of brain tissue in vivo, allowing individual variations in white matter microstructure to be linked with a variety of different clinical outcomes.
The comprehensive analysis identified that common genetic variants explained 41% of the differences in white matter microstructure. Observations showed that these changes in white matter were caused by alterations of gene regulation in oligodendrocytes and other glia. Also, it was found that 151 genomic regions could explain 32% of the heritability in white matter microstructure.
The scientists also identified structural and genetic abnormalities within the white matter that have previously been associated with complex neurological and psychiatric disorders. Furthermore, it was found that 14 white matter microstructure-associated genes were targets for 79 commonly used drugs for heritable diseases, such as Parkinson’s disease and dementia.
The power of studying white matter microstructure
The results from this large-scale GWAS study indicate that strong polygenic influences exist on white matter microstructure. This insight into the heritable nature of white matter has the potential to improve our understanding of neurobiology and, ultimately, the treatment of many diseases that affect the brain.
Many drug targets, commonly for disabling cognitive disorders, have now been shown to exhibit genetic associations with white matter. Therefore, ongoing research is needed to further investigate the significance of white matter within the human brain and enhance neuropharmacology techniques for many neurological disorders.
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