In a report published in the American Journal of Human Genetics, Shulman and collaborators report a two-stage strategy to characterize new genetic determinants of Alzheimer’s disease. They first performed a genomewide association study (GWAS) in an autopsy cohort including 227 participants (91 AD cases, 50 MCI cases, and 86 controls). They selected their best hits for further analyses (p value less than 10-3
At this stage, they coupled this association study with a functional screening, with the postulate that convergence of both association and functional data might allow to restrict false-positive results, the main problem inherent to the genetic analyses, and to finally pick up relevant genes in the AD process.
To perform this functional screening, they used a Drosophila model on the basis of in vivo interactions with the neurotoxicity of tau. They reported that SLC2A14 is a promising gene of interest, associated with AD risk. The Drosophila ortholog was associated with tau toxicity.
The number of cases and controls analyzed in the GWAS...