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

Valentina Escott-Price; Céline 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 Russo; Tricia 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-Thérèse Bihoreau; Christiane Reitz; Florence Pasquier; Paul Hollingworth; Olivier Hanon; Annette L Fitzpatrick; Joseph D Buxbaum; Dominique Campion; Paul K Crane; Clinton Baldwin; Tim Becker; Matthew J Huentelman; Seth Love; John Hardy; United Kingdom Brain Expression Consortium

doi:10.1371/journal.pone.0094661

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

Valentina Escott-Price, Céline 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-Thérèse Bihoreau, Christiane Reitz, Florence Pasquier, Paul Hollingworth, Olivier Hanon, Annette L Fitzpatrick, Joseph D Buxbaum, Dominique Campion, Paul K Crane, Clinton Baldwin, Tim Becker, Matthew J Huentelman, Seth Love, John Hardy, United Kingdom Brain Expression Consortium

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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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.

Original language	English
Pages (from-to)	e94661
Journal	PLoS ONE
Volume	9
Issue number	6
DOIs	https://doi.org/10.1371/journal.pone.0094661
Publication status	Published - 2014

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Cerebrovascular and Dementia Research Group

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Escott-Price, V., Bellenguez, C., Wang, L.-S., Choi, S.-H., Harold, D., Jones, L., Holmans, P., Gerrish, A., Vedernikov, A., Richards, A., DeStefano, A. L., Lambert, J.-C., Ibrahim-Verbaas, C. A., Naj, A. C., Sims, R., Jun, G., Bis, J. C., Beecham, G. W., Grenier-Boley, B., ... United Kingdom Brain Expression Consortium (2014). Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease. PLoS ONE, 9(6), e94661. https://doi.org/10.1371/journal.pone.0094661

@article{c6b58d9fb64e4c7fa78483358b7351b9,

title = "Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease",

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.",

author = "Valentina Escott-Price and C{\'e}line Bellenguez and Li-San Wang and Seung-Hoan Choi and Denise Harold and Lesley Jones and Peter Holmans and Amy Gerrish and Alexey Vedernikov and Alexander Richards and DeStefano, {Anita L} and Jean-Charles Lambert and Ibrahim-Verbaas, {Carla A} and Naj, {Adam C} and Rebecca Sims and Gyungah Jun and Bis, {Joshua C} and Beecham, {Gary W} and Benjamin Grenier-Boley and Giancarlo Russo and Thornton-Wells, {Tricia A} and Nicola Denning and Smith, {Albert V} and Vincent Chouraki and Charlene Thomas and Ikram, {M Arfan} and Diana Zelenika and Vardarajan, {Badri N} and Yoichiro Kamatani and Chiao-Feng Lin and Helena Schmidt and Brian Kunkle and Dunstan, {Melanie L} and Maria Vronskaya and Johnson, {Andrew D} and Agustin Ruiz and Marie-Th{\'e}r{\`e}se Bihoreau and Christiane Reitz and Florence Pasquier and Paul Hollingworth and Olivier Hanon and Fitzpatrick, {Annette L} and Buxbaum, {Joseph D} and Dominique Campion and Crane, {Paul K} and Clinton Baldwin and Tim Becker and Huentelman, {Matthew J} and Seth Love and John Hardy and {United Kingdom Brain Expression Consortium}",

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doi = "10.1371/journal.pone.0094661",

language = "English",

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Escott-Price, V, Bellenguez, C, Wang, L-S, Choi, S-H, Harold, D, Jones, L, Holmans, P, Gerrish, A, Vedernikov, A, Richards, A, DeStefano, AL, Lambert, J-C, Ibrahim-Verbaas, CA, Naj, AC, Sims, R, Jun, G, Bis, JC, Beecham, GW, Grenier-Boley, B, Russo, G, Thornton-Wells, TA, Denning, N, Smith, AV, Chouraki, V, Thomas, C, Ikram, MA, Zelenika, D, Vardarajan, BN, Kamatani, Y, Lin, C-F, Schmidt, H, Kunkle, B, Dunstan, ML, Vronskaya, M, Johnson, AD, Ruiz, A, Bihoreau, M-T, Reitz, C, Pasquier, F, Hollingworth, P, Hanon, O, Fitzpatrick, AL, Buxbaum, JD, Campion, D, Crane, PK, Baldwin, C, Becker, T, Huentelman, MJ, Love, S, Hardy, J & United Kingdom Brain Expression Consortium 2014, 'Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease', PLoS ONE, vol. 9, no. 6, pp. e94661. https://doi.org/10.1371/journal.pone.0094661

TY - JOUR

T1 - Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease

AU - Escott-Price, Valentina

AU - Bellenguez, Céline

AU - Wang, Li-San

AU - Choi, Seung-Hoan

AU - Harold, Denise

AU - Jones, Lesley

AU - Holmans, Peter

AU - Gerrish, Amy

AU - Vedernikov, Alexey

AU - Richards, Alexander

AU - DeStefano, Anita L

AU - Lambert, Jean-Charles

AU - Ibrahim-Verbaas, Carla A

AU - Naj, Adam C

AU - Sims, Rebecca

AU - Jun, Gyungah

AU - Bis, Joshua C

AU - Beecham, Gary W

AU - Grenier-Boley, Benjamin

AU - Russo, Giancarlo

AU - Thornton-Wells, Tricia A

AU - Denning, Nicola

AU - Smith, Albert V

AU - Chouraki, Vincent

AU - Thomas, Charlene

AU - Ikram, M Arfan

AU - Zelenika, Diana

AU - Vardarajan, Badri N

AU - Kamatani, Yoichiro

AU - Lin, Chiao-Feng

AU - Schmidt, Helena

AU - Kunkle, Brian

AU - Dunstan, Melanie L

AU - Vronskaya, Maria

AU - Johnson, Andrew D

AU - Ruiz, Agustin

AU - Bihoreau, Marie-Thérèse

AU - Reitz, Christiane

AU - Pasquier, Florence

AU - Hollingworth, Paul

AU - Hanon, Olivier

AU - Fitzpatrick, Annette L

AU - Buxbaum, Joseph D

AU - Campion, Dominique

AU - Crane, Paul K

AU - Baldwin, Clinton

AU - Becker, Tim

AU - Huentelman, Matthew J

AU - Love, Seth

AU - Hardy, John

AU - United Kingdom Brain Expression Consortium

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

U2 - 10.1371/journal.pone.0094661

DO - 10.1371/journal.pone.0094661

M3 - Article (Academic Journal)

C2 - 24922517

SN - 1932-6203

VL - 9

SP - e94661

JO - PLoS ONE

JF - PLoS ONE

IS - 6

ER -

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

Abstract

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