Researchers Discover 16 New Alzheimer’s Disease Susceptibility Genes

Investigators from Mass General Brigham have conducted a multi-ancestry, whole genome sequencing association study of Alzheimer’s disease and found evidence for 16 new susceptibility genes, expanding the study of Alzheimer’s disease in underrepresented groups. Their results are 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 McCance Center for Brain Health at Massachusetts General Hospital, a founding member of Mass General Brigham, researchers used whole-genome sequencing and a cohort of 49,149 individuals. The study included 12,074 participants who were clinically diagnosed with Alzheimer’s disease and 37,075 diagnosed due to their family history. Participants were from multiple public databases and nearly half were of non-European ancestry. Researchers found 16 novel Alzheimer’s disease-associated genetic signals, highlighting 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, with a double increase of the sample size, including a gene-based rare variant analysis. They also plan to combine the signals of rare variants within genes.

“We were pleasantly surprised to have made this discovery by expanding genetic analyses beyond populations of European ancestry to more diverse populations,” said co-senior author Rudolph Tanzi, PhD, director of the Genetics and Aging Research Unit, 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 disease risk and to new pharmacological and biological targets for treatment and prevention in populations with various ancestries.”

Authorship: In addition to Willett, Waqas, Prokopenko and Tanzi, Mass General Brigham authors include, Younjung Choi, Tiffany Ngai, and Kristina Mullin.

Funding: This work was supported by Cure Alzheimer’s Fund (NIGMS T32GM007748)

Paper cited: Willett JDS et al. “Identification of 16 novel Alzheimer’s loci using multi-ancestry meta-analyses” Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association DOI: 10.1002/alz.14592