July 2, 2021

While gray matter is a common focus in topics of brain structure, white matter also plays a critical role in helping the body process information. It connects regions that send and receive signals, affecting the ability to focus and learn, solve problems, and stay balanced when walking. It’s a significant area of interest for public health experts, since conditions that impact white matter can lead to significant cognitive impairment and increase the risk of long-term neurological problems.

New research from UNC-Chapel Hill suggests that some diseases affecting white matter may be associated with structural and genetic abnormalities in the brain, which sheds further light on the complex genetic relationship between white matter, brain disease and mental health.

Dr. Bingxin Zhao

Dr. Bingxin Zhao

Dr. Tengfei Li

Dr. Tengfei Li

The study, published recently in Science, was led by the Biostatistics and Imaging Genomics Analysis Lab’s Statistics and Signal group (BIG-S2), a collaboration between the UNC Gillings School of Global Public Health and the UNC School of Medicine. The co-first authors were doctoral researcher Bingxin Zhao, PhD, in the Department of Biostatistics and Tengfei Li, PhD, in the Department of Radiology. Additional researchers from the Department of Biostatistics included doctoral students Yue Yang, Xifeng Wang, Tianyou Luo and Ziliang Zhu; and Professors Yun Li, PhD, and Hongtu Zhu, PhD. Professor Zhu serves as the corresponding author on the study.

The research team identified genetic elements that impact white matter differences and located numerous genes associated with white matter. In a perspective piece accompanying the study, the authors suggest that it “presents compelling evidence for the importance of white matter by demonstrating genetic influences on structural connectivity that invoke a host of provocative clinical implications.”

Through a technique known as a genome-wide association study (GWAS), the team analyzed the genetic architecture of brain white matter using diffusion MRI data from 43,802 people that was available in five major data resources. They identified 109 regions associated with white matter microstructure that had not previously been identified through GWAS. These create a broader picture of the influence that multiple genes may have on the structure of white matter.

They also identified genetic correlations between white matter microstructure and a wide range of brain-related traits and diseases. The genetic variations found in the study showed the potential to alter the function of brain cells that generate myelin – the fatty surface that surrounds the neurological pathways in white matter. Such genetic variations could be associated with cognitive disorders, cardiovascular risks, and several neurological and psychiatric diseases.

In addition, they found that 14 white matter-related genes were targets for many commonly used nervous system medications, including anti-psychotics, anti-depressants, anti-convulsants, and medications used to treat Parkinson’s disease, dementia and addictive disorders.

“This large-scale study has improved our understanding of the elaborate genetic architecture of white matter tracts in the human brain,” the researchers wrote. “Moreover, this study uncovered the genetic relationships between white matter and various clinical endpoints. Many drugs commonly used for cognitive disorders have genetic associations with white matter, suggesting that the neuropharmacology of many disorders can potentially be improved by considering the relationship of these medications to white matter.”

For more results on imaging genetics and information on future research, please visit the team’s Brain Imaging Genetics Knowledge Portal.

Contact the UNC Gillings School of Global Public Health communications team at sphcomm@unc.edu.

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