Researchers at Mass General Brigham conducted a multicenter, whole-genome sequencing study of Alzheimer’s disease, finding evidence for 16 new susceptibility genes, expanding Alzheimer’s research in underrepresented groups. Their findings were published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
For the study, co-led by Julian Daniel Sunday Willett, MD, PhD, and Mohammad Waqas of the Genetics and Aging Research Unit and the McCance Center for Brain Health at Massachusetts General Hospital, a founding member of Mass General Brigham, the researchers utilized whole-genome sequencing and a cohort of 49,149 individuals. The study included 12,074 participants who had been clinically diagnosed with Alzheimer’s and 37,075 who had been diagnosed based on their family history. Participants came from several public databases, and nearly half were of non-European ancestry. The researchers found 16 new genetic signals associated with Alzheimer’s disease, underscoring the importance of studying diverse populations. Next, according to co-senior author Dmitry Prokopenko, PhD, the team plans to analyze additional sets of whole-genome sequencing data, doubling the sample size, including a gene-based analysis of rare variants. They also plan to combine signals of rare variants within genes.
“We were pleasantly surprised to make this discovery by expanding the genetic analyses beyond European ancestry populations to more diverse populations,” said co-senior author Dr. Rudolph Tanzi, director of the Genetics and Aging Research Unit of the McCance Center for Brain Health and co-director of the Institute for Neurodegenerative Disease at Massachusetts General Hospital. “We hope this will lead to more accurate predictions of Alzheimer’s risk and new pharmacological and biological targets for treatment and prevention across diverse ancestral populations.”
