A slight difference in DNA could shape some peoples' susceptibility to developing Alzheimer's disease, researchers have found. Experts based at various institutions in Hong Kong found that Chinese participants with longer repeats of a specific gene sequence in their DNA were more likely to have the disease. The association was also noted among European participants, although it was much weaker.
The study was published in the journal Nature Neuroscience on October 12. Researchers have previously identified several genetic variants that are believed to be associated with Alzheimer's risk, and it is understood that those who have a parent or sibling diagnosed with the disease are more likely to develop it than people without those links—although this doesn't mean that person will develop Alzheimer's, it only increases the odds. That said, Alzheimer's does not have a single genetic cause, and is believed instead to be influenced by a combination of genetic, lifestyle and environmental factors.
What the experts set out to understand in this study was whether repeats of certain genetic sequences—rather than specific genetic variants—could influence risk. Rudolph Tanzi, a professor of neurology at Harvard University, told Newsweek that the "potentially important" study "goes beyond the normal single-base genome variants that are tested in the many genome-wide association studies of Alzheimer’s disease." "We know that the common DNA variants that show association with Alzheimer’s in genome-wide association studies account for less than 50 percent of the heritability of Alzheimer’s disease. So finding these types of DNA repeat variants in the genome is very important," he said.
Michael Guo, an assistant professor of neurology and genetics, and a clinician in the University of Pennsylvania Memory Center, told Newsweek: "This is an exciting study that highlights the importance of studying diverse populations and expanding our analyses to include broader sets of spelling errors in our DNA." "Their work may help improve our ability to predict Alzheimer’s disease risk," he added. "Ultimately, by identifying a new gene linked to Alzheimer’s disease, this could spur further work into how FAM193B causes disease and whether it may serve as a drug target." The researchers found that the genetic sequence CCG, which is part of the DNA that controls the gene FAM193B, could hold important clues about certain peoples' odds of developing Alzheimer's disease. A Chinese cohort of over 3,000 people were included in the study—around half of whom had Alzheimer's disease—as well as genetic data and records obtained from UK Biobank (around 2,600 with Alzheimer's and almost 23,000 controls) to see whether the findings were the same among different ancestries.
From 11 of the Chinese participants, the researchers built a more detailed reference of different structural DNA sets and then analyzed the collections of the other DNA readings. They noticed that the CCG DNA string could have repeats from between four to 30 among the participants, and found that those with at least 18 repeats had twice the odds of having Alzheimer's disease than those with no more than 11 repeats. This indicates that repeated strands of the sequence could increase likelihood of having the disease, not a person's lifetime risk of developing the disease.
The finding was also weaker—though still identified—among the European participants' records from UK Biobank, meaning that the estimate among the Chinese cohort cannot be translated directly across different ancestral groups. "This isn’t unexpected, many genetic variants including APOE have different effect sizes in populations of different ancestries," Michael Lutz, a professor of neurology and pathology at Duke University, told Newsweek. APOE is the gene that has been associated with Alzheimer's, and its variant APOE4 is the strongest known genetic risk factor for the disease.
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