Genome Data Confirm SORL1 Gene Linked To Alzheimer's

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Three mutated genes - amyloid precursor protein (APP) and the presenilins (PS1 and PS2) - have been shown to cause rare, early-onset, familial forms of the disease which mostly occur in middle age. A gene variant - apolipoprotein ε4 (APO-ε4) - was the first confirmed risk factor for the common form of late-onset AD, which typically occurs after age 65.

Earlier this year, researchers first linked variations in the gene SORL1 to late-onset AD. The analysis involved 14 collaborating institutions in North America, Europe and Asia, and 6,600 people who donated blood and tissue for genetic typing. To learn more, go to here.

This new study confirms those findings and in a novel way. Lindsay A. Farrer, Ph.D., of the Boston University School of Medicine and colleagues accessed data from a genome-wide association study (GWAS) recently made publicly available online by the Translational Genomics Research Institute (TGen), a nonprofit research institute promoting genomics research. GWAS involves rapidly scanning for markers across the complete set of DNA of many people to find genetic variations related to a particular disease. By analyzing TGen's data on the DNA of 1,408 cases and controls, Dr. Farrer's study replicated the findings of the earlier studies that linked SORL1 data to late-onset AD.

"These results are especially remarkable since this gene was not a focus of the original TGen study which generated the data used to test our hypothesis," Farrer said.

"This is the first example of publicly available data from a genome-wide association study to confirm the identification of a risk factor gene," said Marcelle Morrison-Bogorad, Ph.D., director of the Neuroscience and Neuropsychology Program at NIA. "This shows the tremendous benefit of highly collaborative interaction and rapid data sharing. Sample sharing greatly increases the likelihood of finding new risk factor genes relatively quickly and inexpensively."

Collaboration was a hallmark of the study, with TGen conducting the GWAS using brain tissues and blood samples made available by NIA Alzheimer Center brain banks, NIA-funded investigators, and other collaborating institutes. The Boston University Linux Cluster for Genetic Analysis, funded by the National Center for Research Resources (NCRR) at the NIH, provided Dr. Farrer's group high-speed computer analysis. http://www.sciencedaily.com

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