Researchers report that a variation in the gene ABCA7 causes a twofold increase in the risk of late-onset Alzheimer disease among African Americans. The team, including scientists from the Perelman School of Medicine at the University of Pennsylvania, says this is the largest analysis to date to determine genetic risk associated with late-onset Alzheimer disease (LOAD) specifically in African American individuals.
The Alzheimer Disease Genetics Consortium compared genetic data from 5,896 African Americans over 60 years of age, with and without Alzheimer disease. The association of Alzheimer’s with genotyped and imputed single-nucleotide polymorphisms was assessed in case-control and in family-based datasets. Results from individual datasets were combined to perform an inverse variance-weighted meta-analysis, first with genome-wide analyses and subsequently with gene-based tests for previously reported loci.
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). These are genotypes also associated with increased risk among individuals of European ancestry, but the association with ABCA7 was 60% stronger among African Americans than what has been observed among individuals of European ancestry.
“While the genotypes are similar between groups, the strength of risk is significantly different,” says Gerard Schellenberg, Ph.D., professor of pathology and laboratory medicine in the Perelman School. “ABCA7 was previously identified to be weakly involved in the risk of Alzheimer disease among nonhispanics 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% of people at age 65 years to more than 30% of people older than 80 years. As much as 20% of the disease-attributable risk is related to the APOe4 gene variation.
The researchers note that if their study can be validated and replicated in additional studies, these findings may have “major implications for developing targets for genetic testing, prevention, and treatment.”
The study appears in the April 10 issue of JAMA, in a paper titled “Variants in the ATP-Binding Cassette Transporter (ABCA7), Apolipoprotein E ε4,and the Risk of Late-Onset Alzheimer Disease in African Americans”.