Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease

Valentina Escott-Price, Celine Bellenguez, Li-San Wang, Seung-Hoan Choi, Denise Harold, Lesley Jones, Peter Holmans, Amy Gerrish, Alexey Vedernikov, Alexander Richards, Anita L. DeStefano, Jean-Charles Lambert, Carla A. Ibrahim-Verbaas, Adam C. Naj, Rebecca Sims, Gyungah Jun, Joshua C. Bis, Gary W. Beecham, Benjamin Grenier-Boley, Giancarlo RussoTricia A. Thornton-Wells, Nicola Denning, Albert V. Smith, Vincent Chouraki, Charlene Thomas, M. Arfan Ikram, Diana Zelenika, Badri N. Vardarajan, Yoichiro Kamatani, Chiao-Feng Lin, Helena Schmidt, Brian Kunkle, Melanie L. Dunstan, Maria Vronskaya, Andrew D. Johnson, Agustin Ruiz, Marie-Therese Bihoreau, Christiane Reitz, Florence Pasquier, Paul Hollingworth, Olivier Hanon, Annette L. Fitzpatrick, Joseph D. Buxbaum, Dominique Campion, Paul K. Crane, Clinton Baldwin, Tim Becker, Simon Lovestone, Petra Proitsi, John F. Powell, United Kingdom Brain Expression

Research output: Contribution to journalArticlepeer-review

97 Citations (Scopus)

Abstract

Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls.

Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci.

Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.

Original languageEnglish
Article numbere94661
Number of pages13
JournalPL o S One
Volume9
Issue number6
DOIs
Publication statusPublished - 12 Jun 2014

Keywords

  • GENOME SCAN METAANALYSIS
  • IDENTIFIES VARIANTS
  • BIPOLAR DISORDER
  • COMMON VARIANTS
  • COMPLEX TRAITS
  • LEIGH-SYNDROME
  • ASSOCIATION
  • EXPRESSION
  • TP53INP1
  • CANCER

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