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Study Finds New Genetic Risk Factors for Alzheimer’s Disease in Blacks

Black Americans are twice as likely as whites to develop Alzheimer’s but have been underrepresented in genetic research about the disease.

Until recently, researchers thought that when genes are linked to Alzheimer’s in whites, that finding could be extrapolated to other groups, says Christiane Reitz, MD, PhD, associate professor of neurology at Columbia University Vagelos College of Physicians and Surgeons and of epidemiology at Mailman School of Public Health.

“And so, there was little conscious effort to make sure that Black, Hispanic, or Asian Americans, were adequately represented in genome-wide association studies.”

But it has become clear, she says, “that there are genetic variations in the disease from group to group and that these studies need to be more inclusive.”

Reitz was one of the first researchers to look for the genetic factors that raise the risk of Alzheimer’s in Blacks, and her most recent study—conducted with colleagues Margaret Pericak-Vance, PhD, and Brian Kunkle, PhD, at the University of Miami on behalf of the Alzheimer Disease Genetics Consortium—is the largest such study to date.

CUIMC News recently spoke with Reitz about the importance of the findings.

Why are Blacks twice as likely to develop Alzheimer’s compared to whites?

We’re not certain. We know that Blacks have higher rates of vascular disease, such as diabetes, stroke, and hypertension, which are risk factors for Alzheimer’s. But that’s not the whole story. Genetics also plays a role, which we’re just beginning to understand. Studies like this one may provide some answers.

What's new in this study?

In this study, which included more than 8,000 participants, we identified several new genetic risk factors for Alzheimer’s in Blacks.

These genes—combined with several new genes recently identified by our group in a largely white population—suggest that the pathways that contribute to Alzheimer’s in Blacks are at least partly similar to those in non-Hispanic whites. These pathways involve immunity, lipid processing, and intracellular trafficking. 

However, we found that some of the genetic variants in those pathways are different in Blacks than in whites.

We also identified a possible new disease pathway in Blacks related to kidney function, suggesting a novel mechanism for Alzheimer’s. We don’t yet know the significance of these newly identified genetic variants or of this new disease pathway.

Will these findings affect clinical care?

Not yet. First, we need to confirm the findings in independent genetic and experimental studies.

And we need to pinpoint the specific causative mutations in the genes, which we’re now doing by sequencing the genomes of a large set of people.

Identifying these mutations will be critical in paving the way toward disease screening, prevention, and new treatments.

The findings also have implications for predicting each individual’s chance of developing Alzheimer’s. In the future we think that polygenic risk scores—which take dozens of genetic risk factors into account—can help us identify those most at risk. Our findings tell us that we likely will need different risk scores for different ethnicities, since the genetic risk factors vary somewhat from group to group.      

Do we need more genetic studies with Black participants?

The way genomic studies work, the larger the sample size, the more likely you are to detect statistically meaningful genetic differences between populations. 

So right now, we’re developing studies with even larger numbers of Black participants.

The more we understand these differences, the better we will able to assess an individual’s risk for the disease and develop precision medicine approaches. 


More information

The findings were published Oct. 19 in JAMA Neurology in a paper titled “Novel Alzheimer Disease Risk Loci and Pathways in African American Individuals Using the African Genome Resources Panel.”

Christiane Reitz also is a member of the Gertrude H. Sergievsky Center and the Taub Institute for Research on Alzheimer's Disease and the Aging Brain at Columbia.

The study was supported by the NIH (see paper for full list of grants).

Dr. Reitz reports no conflicts of interest.