Initial Assessment of the Pathogenic Mechanisms of the Recently Identified Alzheimer Risk Loci. (30th January 2013)

• Record Type: Journal Article
• Authors: Holton, Patrick; Ryten, Mina; Nalls, Michael; Trabzuni, Daniah; Weale, Michael E.; Hernandez, Dena; Crehan, Helen; Gibbs, J. Raphael; Mayeux, Richard; Haines, Jonathan L.; Farrer, Lindsay A.; Pericak‐Vance, Margaret A.; Schellenberg, Gerard D.; Ramirez‐Restrepo, Manuel; Engel, Anzhelika; Myers, Amanda J.; Corneveaux, Jason J.; Huentelman, Matthew J.; Dillman, Allissa; Cookson, Mark R.; Reiman, Eric M.; Singleton, Andrew; Hardy, John; Guerreiro, Rita
• Is Part Of: Annals of human genetics. Volume 77:Number 2(2013:Mar.)
• Page Start: 85
• Page End: 105
• Publication Date: 2013-01-30
• Subjects: Human genetics -- Periodicals; 599.935
• DOI: 10.1111/ahg.12000
• Languages: English
• ISSNs: 0003-4800

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p>Recent genome wide association studies have identified <italic>CLU</italic>, <italic>CR1</italic>, <italic>ABCA7 BIN1</italic>, <italic>PICALM</italic> and <italic>MS4A6A</italic>/<italic>MS4A6E</italic> in addition to the long established <italic>APOE</italic>, as loci for Alzheimer's disease. We have systematically examined each of these loci to assess whether common coding variability contributes to the risk of disease. We have also assessed the regional expression of all the genes in the brain and whether there is evidence of an eQTL explaining the risk. In agreement with other studies we find that coding variability may explain the <italic>ABCA7</italic> association, but common coding variability does not explain any of the other loci. We were not able to show that any of the loci had eQTLs within the power of this study. Furthermore the regional expression of each of the loci did not match the pattern of brain regional distribution in Alzheimer pathology. Although these results are mainly negative, they allow us to start defining more realistic alternative approaches to determine the role of all the genetic loci involved in Alzheimer's disease.</p> </abstract>