NIH’ers Identify Large Genetic Changes that Contribute to Dementia Risk

NIH scientists have identified new genetic risk factors for two types of non-Alzheimer’s dementia. The findings were published in Cell Genomics and detail how researchers identified large-scale DNA changes, known as structural variants, by analyzing thousands of DNA samples. 

The team discovered several structural variants that could be risk factors for Lewy body dementia and frontotemporal dementia. The project was a collaborative effort between scientists at NINDS and NIA.

Structural variants have been implicated in a variety of neurological disorders. Unlike more commonly studied mutations, which often affect one or a few DNA building blocks called nucleotides, structural variants represent at least 50 but often hundreds, or even thousands, of nucleotides at once, making them more challenging to study.

“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 Dr. Sonja Scholz, investigator in the neurogenetics branch of NINDS and senior author of the study.

By combining cutting-edge computer algorithms capable of mapping structural variations across the whole genome with machine learning, the research team analyzed whole-genome data from thousands of patient samples and several thousand unaffected controls.

“From a genetics standpoint, this is a very exciting finding,” said Scholz. “It provides a point of reference for cell biology and animal model studies and possibly down the road, a target for intervention.”