Apr 9, 2013

Genes Associated With Alzheimer Disease Among African Americans and Individuals of European Ancestry

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The data for the analysis came from nearly 6,000 African-Americans who were over age 60 and had participated in studies at 18 medical centers.

The researchers calculated that ABCA7 increased Alzheimer’s risk by about 80 percent in African-Americans, compared with about 10 percent to 20 percent in people of European ancestry.

The researchers’ paper was published online on Tuesday in The Journal of the American Medical Association.

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Study Finds Similarity in Genes Associated With Alzheimer Disease Among African Americans and Individuals of European Ancestry

Alzheimer's Disease
“Late-onset Alzheimer disease (LOAD) is the most common cause of dementia, increasing in frequency from 1 percent at age 65 years to more than 30 percent for people older than 80 years,” according to background information in the article. The incidence of LOAD among African Americans is higher than among whites living in the same community.

“Genetic variants associated with susceptibility to late-onset Alzheimer disease are known for individuals of European ancestry, but whether the same or different variants account for the genetic risk of Alzheimer disease in African American individuals is unknown. Identification of disease-associated variants helps identify targets for genetic testing, prevention, and treatment.”

Christiane Reitz, M.D., Ph.D., of Columbia University, New York, and colleagues conducted a study to identify genetic variants associated with LOAD in African Americans.

The Alzheimer Disease Genetics Consortium (ADGC) assembled multiple data sets representing a total of 5,896 African Americans (1,968 case participants, 3,928 control participants) 60 years or older that were collected between 1989 and 2011 at multiple sites.

The association of Alzheimer disease with genotyped and imputed single-nucleotide polymorphisms (SNPs; DNA sequence variations that occur when a single nucleotide in the genome sequence is altered) was assessed in case-control and in family-based data sets.

The researchers found that the genotypes with the strongest association with the risk of LOAD among African Americans were ABCA7 (odds ratio, 1.8) and APOE (odds ratio, 2.3), genotypes also associated with increased risk among individuals of European ancestry.

However, the association with ABCA7 was 60 percent stronger that than observed among individuals of European ancestry.
“If validated by future replication and functional studies, identification of ABCA7 as a risk gene in LOAD among African Americans not only may help elucidate the disease etiology but also may have major implications for developing targets for genetic testing, prevention, and treatment,” the authors write.
“Identification of the genetic risk variants by resequencing and validation by functional studies would allow refinement of risk estimates and diagnostic and predictive testing protocols specific for African Americans.”
Editorial: Genome-Wide Association Studies, Alzheimer Disease, and Understudied Populations

In an accompanying editorial, Robert L. Nussbaum, M.D., of the University of California, San Francisco, writes about the significance of the findings in this study.

“First, of the many hundreds of genome-wide association studies (GWASs) reported in the National Human Genome Research Institute's Catalog of Published Genome-Wide Association Studies, only a small fraction involve African American populations.

Pursuing research in an understudied ethnic group is important for scientific and for ethical reasons.

Second, replicating an association for the same alleles in different ethnic groups strengthens the case for these variants being important in increasing disease susceptibility.

Third, the strong replication of the association between variants in 2 genes involved in lipid metabolism underscores how GWASs-can point to pathways that play a role in complex diseases.

Proving the functional importance of these genes and variants, however, must await more direct functional studies.”

Source JAMA

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