Genetic variability in response to Aβ deposition influences Alzheimer’s risk

Salih, D. A.; Bayram, S.; Guelfi, M. S.; Reynolds, R. H.; Shoai, M.; Ryten, M.; Brenton, J.; Zhang, D.; Matarin, M.; Botia, J.; Shah, R.; Brookes, K.; Guetta-Baranes, T.; Morgan, K.; Bellou, E.; Cummings, D. M.; Hardy, J.; Edwards, F. A.; Escott-Price, V.

doi:10.1101/437657

bioRxiv · 10.1101/437657

Genetic variability in response to Aβ deposition influences Alzheimer’s risk

Salih, D. A.·Bayram, S.·Guelfi, M. S.·Reynolds, R. H.·Shoai, M.·Ryten, M.·Brenton, J.·Zhang, D.·Matarin, M.·Botia, J.·Shah, R.·Brookes, K.·Guetta-Baranes, T.·Morgan, K.·Bellou, E.·Cummings, D. M.·Hardy, J.·Edwards, F. A.·Escott-Price, V.

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Abstract

Genetic analysis of late-onset Alzheimers disease risk has previously identified a network of largely microglial genes that form a transcriptional network. In transgenic mouse models of amyloid deposition we have previously shown that the expression of many of the mouse orthologs of these genes are co-ordinately up-regulated by amyloid deposition. Here we investigate whether systematic analysis of other members of this mouse amyloid-responsive network predicts other Alzheimers risk loci. This statistical comparison of the mouse amyloid-response network with Alzheimers disease genome-wide association studies identifies 5 other genetic risk loci for the disease (OAS1, CXCL10, LAPTM5, ITGAM and LILRB4). This work suggests that genetic variability in the microglial response to amyloid deposition is a major determinant for Alzheimers risk.\n\nOne Sentence SummaryIdentification of 5 new risk loci for Alzheimers by statistical comparison of mouse A{beta} microglial response with gene-based SNPs from human GWAS

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Salih, D. A., Bayram, S., Guelfi, M. S., Reynolds, R. H., Shoai, M., Ryten, M., Brenton, J., Zhang, D., Matarin, M., Botia, J., Shah, R., Brookes, K., Guetta-Baranes, T., Morgan, K., Bellou, E., Cummings, D. M., Hardy, J., Edwards, F. A., Escott-Price, V.. 2018-10-08. Genetic variability in response to Aβ deposition influences Alzheimer’s risk. https://doi.org/10.1101/437657

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