April 10, 2013

Alzheimer Gene ABCA7 Significantly Increases Late-Onset Risk Among African Americans

Genetic study of late-onset Alzheimer disease in African Americans identifies unique risk levels

A variation in the gene ABCA7 causes a twofold increase in the risk of late onset Alzheimer disease among African Americans, according to a meta-analysis by a team of researchers including experts from the Perelman School of Medicine at the University of Pennsylvania. This is the largest analysis to date to determine genetic risk associated with late-onset Alzheimer disease (LOAD) specifically in African American individuals. The study appears in the April 10 issue of JAMA, a genomics theme issue.

The Alzheimer Disease Genetics Consortium (ADGC) — led by Gerard Schellenberg, PhD, professor of Pathology and Laboratory Medicine in the Perelman School of Medicine — compared genetic data from nearly 6,000 African Americans over 60 years of age, with and without Alzheimer disease. 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. The association with ABCA7 was 60 percent stronger among African Americans than it had been observed among individuals of European ancestry.

"While the genotypes are similar between groups, the strength of risk is significantly different," said Schellenberg. "ABCA7 was previously identified to be weakly involved in the risk of Alzheimer disease among non-hispanics of European ancestry. Among African Americans, however, the gene is associated with a much stronger risk of late-onset Alzheimer disease."

African Americans have a higher incidence of late-onset AD, which affects 1 percent of people at age 65 years to more than 30 percent of people older than 80 years. As much as 20 percent of the disease-attributable risk is related to the APOe4 gene variation.

Researchers note that, if the study can be validated and replicated in additional studies, these findings may have "major implications for developing targets for genetic testing, prevention, and treatment."


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