Scientists at the National Institutes of Health (NIH) leveraged cutting-edge technology to identify genetic risk factors for FTD and Lewy body dementia in a study published earlier this year in Cell Genomics.

NIH’s study focused on “structural variants” – segments of DNA above a specific size that have been copied, deleted, moved, or otherwise altered. While structural variants constitute a significant source of diversity in genetics, growing evidence shows they play a considerable role in the onset of neurodegenerative disorders. For example, the study notes that the discovery of repeats of C9orf72 was crucial in FTD and ALS being put on the same clinical spectrum.

“If you imagine that our entire genetic code is a book, a structural variant would be a paragraph, page, or even an entire chapter that has been removed, duplicated, or inserted in the wrong place,” said Sonja W. Scholz, MD, PhD, a researcher at the National Institute of Neurological Disorders and Stroke, and a senior author of the study.

Previously, most studies on structural variants were tied to specific disease-causing genetic mutations, such as C9orf72 or MAPT. As the authors note, advancements in technologies like detection algorithms have made broader genome-wide studies much more feasible.

The authors applied these advancements to map the structural variants in a large group of participants. By doing so, they hoped to identify common structural variants that moderate the risks of neurodegeneration and to identify rare variants in disease-causing genes.

Using a “multi-algorithm pipeline” to analyze data, the NIH researchers identified known variants associated with C9orf72 and MAPT and successfully identified rare structural variants associated with FTD and ALS.

To help address the lack of data on structural variants, the researchers generated a catalog using the data they obtained and made it available for other researchers to use in their own work, along with the code they used to conduct the analysis. The study’s authors noted that these resources could make complex genetic data more easily available, accelerating the pace of new discoveries.

“Research to unravel the intricate genetic architecture of neurodegenerative diseases is resulting in significant advances in scientific understanding,” said Bryan J. Traynor, MD, PhD, a senior investigator at the National Institute on Aging. “With each discovery, we shed light on the mechanisms behind neuronal cell death or dysfunction, paving the way for precision medicine to combat these debilitating and fatal disorders.”

Want to learn more about the genetics of FTD? Visit our FTD Genetics and You page.

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