@article{a4e75264fef44d26a6f8eee0a3660ead,
title = "Functional screening of alzheimer pathology genome-wide association signals in drosophila",
abstract = "We have leveraged a Drosophila model relevant to Alzheimer disease (AD) for functional screening of findings from a genome-wide scan for loci associated with a quantitative measure of AD pathology in humans. In six of the 15 genomic regions evaluated, we successfully identified a causal gene for the association, on the basis of in vivo interactions with the neurotoxicity of Tau, which forms neurofibrillary tangles in AD. Among the top results, rs10845990 within SLC2A14, encoding a glucose transporter, showed evidence of replication for association with AD pathology, and gain and loss of function in glut1, the Drosophila ortholog, was associated with suppression and enhancement of Tau toxicity, respectively. Our strategy of coupling genome-wide association in humans with functional screening in a model organism is likely to be a powerful approach for gene discovery in AD and other complex genetic disorders.",
author = "Shulman, {Joshua M.} and Portia Chipendo and Chibnik, {Lori B.} and Cristin Aubin and Dong Tran and Keenan, {Brendan T.} and Kramer, {Patricia L.} and Schneider, {Julie A.} and Bennett, {David A.} and Feany, {Mel B.} and {De Jager}, {Philip L.}",
note = "Funding Information: We are grateful to our colleagues, Lei Yu and Sue Leurgans, for assistance with statistical analyses. We thank Christian Klambt, Jimena Sierralta, and Hiroshi Nakato for generously providing Drosophila stocks. We are grateful Dr. Bradley Hyman and Chris Cotsapas for comments on the manuscript and valuable discussion. We also thank the Bloomington Drosophila stock center, the Vienna Drosophila RNAi Center (VDRC), and the Harvard Transgenic RNAi Project (TRiP, NIH/NIGMS R01GM084947) for providing fly stocks. J.M.S. is supported by NIH grant K08AG034290 and by the Clinical Investigator Training Program: Beth Israel Deaconess Medical Center – Harvard/MIT Health Sciences and Technology, in collaboration with Pfizer Inc. and Merck & Co. M.B.F. is supported by the Ellison Medical Foundation. The authors also thank the participants of the Religious Orders Study and the Rush Memory and Aging Project, which were supported by NIH grants P30AG10161, R01AG15819, and R01AG17917. ",
year = "2011",
month = feb,
day = "11",
doi = "10.1016/j.ajhg.2011.01.006",
language = "English (US)",
volume = "88",
pages = "232--238",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "2",
}