Summary: A large whole-genome sequencing study has uncovered 16 new genes linked to Alzheimer’s disease, expanding genetic research beyond European ancestry. Researchers analyzed data from 49,149 individuals, nearly half of whom were from underrepresented populations, to improve understanding of genetic risk factors.
The findings highlight the importance of studying diverse groups for more accurate risk prediction and better-targeted treatments. Next, scientists plan to double the sample size and analyze rare genetic variants to refine their understanding of Alzheimer’s progression.
Key Facts
- New Genetic Discoveries: Researchers identified 16 novel genes linked to Alzheimer’s disease.
- Diverse Representation: Nearly half of the 49,149 study participants were from non-European ancestry.
- Future Research: Scientists aim to expand the study and analyze rare gene variants for deeper insights.
Source: Mass General
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.”
About this genetics and Alzheimer’s disease research news
Author: Brandon Chase
Source: Mass General
Contact: Brandon Chase – Mass General
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Identification of 16 novel Alzheimer’s loci using multi-ancestry meta-analyses” by Julian Daniel Sunday Willett et al. Alzheimer’s & Dementia
Abstract
Identification of 16 novel Alzheimer’s loci using multi-ancestry meta-analyses
INTRODUCTION
Alzheimer’s disease (AD) is the most prevalent form of dementia. While many AD-associated genetic determinants have been identified, few studies have analyzed individuals of non-European ancestry.
METHODS
We conducted a multi-ancestry genome-wide association study (GWAS) of clinically diagnosed AD and AD-by-proxy using whole genome sequencing data from the National Institute on Aging Genetics of Alzheimer’s Disease Data Storage Site (NIAGADS), National Institute of Mental Health, UK Biobank (UKB), and All of Us (AoU) consisting of 49,149 cases (12,074 clinically diagnosed and 37,075 AD-by-proxy) and 383,225 controls. Nearly half of NIAGADS and AoU participants were of non-European ancestry.
RESULTS
For clinically diagnosed AD, we identified 14 new loci—five common (FBN2/SCL27A6, AC090115.1, DYM, KCNG1/AL121785.1, TIAM1) and nine rare (VWA5B1, RNU6-755P/LMX1A, MOB1A, MORC1-AS1, LINC00989, PDE4D, RNU2-49P/CDO1, NEO1, and SLC35G3/AC022916.1). Meta-analysis of UKB and AoU AD-by-proxy cases yielded two new rare loci (RPL23/LASP1 and CEBPA/AC008738.6), also nominally significant in NIAGADS.
DISCUSSION
In summary, we provide evidence for 16 novel AD loci and advocate for more studies using whole genome sequencing–based GWAS of diverse cohorts.
