Initial Assessment of the Pathogenic Mechanisms of the Recently Identified Alzheimer Risk Loci

Patrick Holton, Mina Ryten, Michael Nalls, Daniah Trabzuni, Michael E. Weale, Dena Hernandez, Helen Crehan, J. Raphael Gibbs, Richard Mayeux, Jonathan L. Haines, Lindsay A. Farrer, Margaret A Pericak-Vance, Gerard D. Schellenberg, Manuel Ramirez-Restrepo, Anzhelika Engel, Amanda J Myers, Jason J. Corneveaux, Matthew J. Huentelman, Allissa Dillman, Mark R. CooksonEric M. Reiman, Andrew Singleton, John Hardy, Rita Guerreiro

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Recent genome wide association studies have identified CLU, CR1, ABCA7 BIN1, PICALM and MS4A6A/MS4A6E in addition to the long established APOE, 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 ABCA7 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.

Original languageEnglish
Pages (from-to)85-105
Number of pages21
JournalAnnals of Human Genetics
Volume77
Issue number2
DOIs
StatePublished - Mar 1 2013

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Alzheimer Disease
Genetic Loci
Genome-Wide Association Study
Brain
Pathology
Gene Expression

Keywords

  • Alzheimer's disease
  • Genetic risk
  • GWAS

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Holton, P., Ryten, M., Nalls, M., Trabzuni, D., Weale, M. E., Hernandez, D., ... Guerreiro, R. (2013). Initial Assessment of the Pathogenic Mechanisms of the Recently Identified Alzheimer Risk Loci. Annals of Human Genetics, 77(2), 85-105. https://doi.org/10.1111/ahg.12000

Initial Assessment of the Pathogenic Mechanisms of the Recently Identified Alzheimer Risk Loci. / 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.

In: Annals of Human Genetics, Vol. 77, No. 2, 01.03.2013, p. 85-105.

Research output: Contribution to journalArticle

Holton, P, Ryten, M, Nalls, M, Trabzuni, D, Weale, ME, Hernandez, D, Crehan, H, Gibbs, JR, Mayeux, R, Haines, JL, Farrer, LA, Pericak-Vance, MA, Schellenberg, GD, Ramirez-Restrepo, M, Engel, A, Myers, AJ, Corneveaux, JJ, Huentelman, MJ, Dillman, A, Cookson, MR, Reiman, EM, Singleton, A, Hardy, J & Guerreiro, R 2013, 'Initial Assessment of the Pathogenic Mechanisms of the Recently Identified Alzheimer Risk Loci', Annals of Human Genetics, vol. 77, no. 2, pp. 85-105. https://doi.org/10.1111/ahg.12000
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. / Initial Assessment of the Pathogenic Mechanisms of the Recently Identified Alzheimer Risk Loci. In: Annals of Human Genetics. 2013 ; Vol. 77, No. 2. pp. 85-105.
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