It is known that Alzheimer’s disease is more common in African-Americans than Caucasians, however, the Alzheimer’s disease genetic risk profile for African-Americans is poorly understood. While more than 20 genes have been identified as risk factors for Alzheimer’s disease in Caucasians, fewer than five have been identified for African-Americans. Now, a study from researchers at Boston University identifies two new genetic risk factors for Alzheimer’s disease among African-Americans. The team state that their findings may lead to the development of new therapies specifically targeting those genes. The study is published in the journal Alzheimer’s and Dementia.
Previous studies analysing the genome-wide association of Alzheimer’s disease in more than 5,500 African-Americans identified two genetic risk factors for Alzheimer’s disease. This study looked at genetic variants across subjects’ entire genome, and compared their frequency in cases versus controls. Therefore, the lab used these same subjects and added additional Alzheimer’s disease risk information such as smoking status, diabetes status, education level to their statistical modeling. The current study identifies two new genes, namely COBL and SLC10A2, associated with risk of Alzheimer’s disease in African-Americans.
The current study conducted a genome-wide association study in African-Americans employing informed conditioning in 1825 late-onset Alzheimer’s disease cases and 3784 cognitively normal controls. The group analysed Alzheimer’s risk factors conditioned on age, sex, diabetes status, current smoking status, and educational attainment.
Results show that by using this conditioning approach the researchers were able to assess the association between the posterior liability and a genome-wide set of single-nucleotide polymorphisms, controlling for APOE and ABCA7, identified previously. Data findings show that two new genetic risk factors were identified at novel loci, upstream of COBL, and downstream of SLC10A2. The lab state that the methodology employed allowed them to make an important discovery without investing more money in genotyping or more effort to recruit volunteers. They conclude that a similar methodology could be used for many other diseases to make new genetic discoveries without new large investments.
The team surmise their study shows that an informed conditioning approach can detect late-onset Alzheimer’s disease genetic associations in African-Americans not identified by traditional genome-wide association. For the future, the researchers state that there are currently no medications for Alzheimer’s disease that slow or stop the progression of the disease. They go on to add that the genes identified are potential targets for new disease-modifying Alzheimer’s disease drug therapies.