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Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease

Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease
Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease

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 = 1.4×10-6) and 14 (IGHV1-67 p = 7.9×10-8) 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.

Alzheimer Disease, Carrier Proteins, Case-Control Studies, Genome-Wide Association Study, Heat-Shock Proteins, Humans, Polymorphism, Single Nucleotide, Receptors, Antigen, B-Cell, Journal Article, Research Support, N.I.H., Extramural
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Escott-Price, Valentina, Bellenguez, Céline, Wang, Li-San, Choi, Seung-Hoan, Harold, Denise, Jones, Lesley, Holmans, Peter, Gerrish, Amy, Vedernikov, Alexey, Richards, Alexander, DeStefano, Anita L, Lambert, Jean-Charles, Ibrahim-Verbaas, Carla A, Naj, Adam C, Sims, Rebecca, Jun, Gyungah, Bis, Joshua C, Beecham, Gary W, Grenier-Boley, Benjamin, Russo, Giancarlo, Thornton-Wells, Tricia A, Denning, Nicola, Smith, Albert V, Chouraki, Vincent, Thomas, Charlene, Ikram, M Arfan, Zelenika, Diana, Vardarajan, Badri N, Kamatani, Yoichiro, Lin, Chiao-Feng, Schmidt, Helena, Kunkle, Brian, Dunstan, Melanie L, Vronskaya, Maria, Johnson, Andrew D, Ruiz, Agustin, Bihoreau, Marie-Thérèse, Reitz, Christiane, Pasquier, Florence, Hollingworth, Paul, Hanon, Olivier, Fitzpatrick, Annette L, Buxbaum, Joseph D, Campion, Dominique, Crane, Paul K, Baldwin, Clinton, Becker, Tim, Gudnason, Vilmundur, Cruchaga, Carlos and Holmes, Clive , United Kingdom Brain Expression Consortium (2014) Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease. PLoS ONE, 9 (6), e94661. (doi:10.1371/journal.pone.0094661).

Record type: Article

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 = 1.4×10-6) and 14 (IGHV1-67 p = 7.9×10-8) 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.

Full text not available from this repository.

More information

Published date: 12 June 2014
Keywords: Alzheimer Disease, Carrier Proteins, Case-Control Studies, Genome-Wide Association Study, Heat-Shock Proteins, Humans, Polymorphism, Single Nucleotide, Receptors, Antigen, B-Cell, Journal Article, Research Support, N.I.H., Extramural

Identifiers

Local EPrints ID: 416130
URI: https://eprints.soton.ac.uk/id/eprint/416130
ISSN: 1932-6203
PURE UUID: c4aa994c-45d5-4a29-b3b4-ef93bf475363
ORCID for Clive Holmes: ORCID iD orcid.org/0000-0003-1999-6912

Catalogue record

Date deposited: 05 Dec 2017 17:30
Last modified: 15 Aug 2019 00:49

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Contributors

Author: Valentina Escott-Price
Author: Céline Bellenguez
Author: Li-San Wang
Author: Seung-Hoan Choi
Author: Denise Harold
Author: Lesley Jones
Author: Peter Holmans
Author: Amy Gerrish
Author: Alexey Vedernikov
Author: Alexander Richards
Author: Anita L DeStefano
Author: Jean-Charles Lambert
Author: Carla A Ibrahim-Verbaas
Author: Adam C Naj
Author: Rebecca Sims
Author: Gyungah Jun
Author: Joshua C Bis
Author: Gary W Beecham
Author: Benjamin Grenier-Boley
Author: Giancarlo Russo
Author: Tricia A Thornton-Wells
Author: Nicola Denning
Author: Albert V Smith
Author: Vincent Chouraki
Author: Charlene Thomas
Author: M Arfan Ikram
Author: Diana Zelenika
Author: Badri N Vardarajan
Author: Yoichiro Kamatani
Author: Chiao-Feng Lin
Author: Helena Schmidt
Author: Brian Kunkle
Author: Melanie L Dunstan
Author: Maria Vronskaya
Author: Andrew D Johnson
Author: Agustin Ruiz
Author: Marie-Thérèse Bihoreau
Author: Christiane Reitz
Author: Florence Pasquier
Author: Paul Hollingworth
Author: Olivier Hanon
Author: Annette L Fitzpatrick
Author: Joseph D Buxbaum
Author: Dominique Campion
Author: Paul K Crane
Author: Clinton Baldwin
Author: Tim Becker
Author: Vilmundur Gudnason
Author: Carlos Cruchaga
Author: Clive Holmes ORCID iD

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