Two new genetic loci associated with Alzheimer's disease have been identified on chromosomes 2 and 19, according to researchers.
These loci will not help in identifying people at risk for AD. But they do implicate particular biological pathways that eventually could become important targets for intervention, said Dr. Sudha Seshadri of Boston University and her associates.
The researchers explored the genetics of late-onset Alzheimer's disease by performing a three-stage analysis of data accrued in several genome-wide association studies involving more than 35,000 subjects (JAMA 2010;303:1832-40).
In the first stage, they combined data from nine sources, including the Mayo AD genome-wide association study. From these sources they identified 2,708 candidate single nucleotide polymorphisms (SNPs) for further study. In the second stage of the study, Dr. Seshadri and her colleagues combined the most promising results from these genome-wide association studies and a large European data source to narrow the search to the 38 most suggestive SNPs found in 10 loci.
Finally, they combined this data with previously gathered data from the Genetic and Environmental Risk in AD 1 consortium and identified three loci already known to be associated with AD (APOE, CLU, and PICALM) as well as two novel loci on chromosomes 2 and 19.
In an editorial, Nancy L. Pedersen, Ph.D., of the Karolinska Institutet, Stockholm, said that the investigators' three-stage approach was exemplary but that considerable work would be needed to understand the “complex nexus by which these genes contribute to pathogenesis.”
Disclosures: The funding sources for this study were not available at press time. Neither Dr. Seshadri and her coauthors nor Dr. Pedersen reported conflicts of interest.