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; Vilmundur Gudnason; Carlos Cruchaga; David Craig; Najaf Amin; Claudine Berr; Oscar L. Lopez; Philip L. De Jager; Vincent Deramecourt; Janet A. Johnston; Denis Evans; Simon Lovestone; Luc Letenneur; Isabel Hernández; David C. Rubinsztein; Gudny Eiriksdottir; Kristel Sleegers; Alison M. Goate; Nathalie Fiévet; Matthew J. Huentelman; Michael Gill; Kristelle Brown; M. Ilyas Kamboh; Lina Keller; Pascale Barberger-Gateau; Bernadette McGuinness; Eric B. Larson; Amanda J. Myers; Carole Dufouil; Stephen Todd; David Wallon; Seth Love; Ekaterina Rogaeva; John Gallacher; Peter St George-Hyslop; Jordi Clarimon; Alberto Lleo; Anthony Bayer; Debby W. Tsuang; Lei Yu; Magda Tsolaki; Paola Bossù; Gianfranco Spalletta; Petra Proitsi; John Collinge; Sandro Sorbi; Florentino Sanchez Garcia; Nick C. Fox; John Hardy; Maria Candida Deniz Naranjo; Paolo Bosco; Robert Clarke; Carol Brayne; Daniela Galimberti; Elio Scarpini; Ubaldo Bonuccelli; Michelangelo Mancuso; Gabriele Siciliano; Susanne Moebus; Patrizia Mecocci; Maria Del Zompo; Wolfgang Maier; Harald Hampel; Alberto Pilotto; Ana Frank-García; Francesco Panza; Vincenzo Solfrizzi; Paolo Caffarra; Benedetta Nacmias; William Perry; Manuel Mayhaus; Lars Lannfelt; Hakon Hakonarson; Sabrina Pichler; Minerva M. Carrasquillo; Martin Ingelsson; Duane Beekly; Victoria Alvarez; Fanggeng Zou; Otto Valladares; Steven G. Younkin; Eliecer Coto; Kara L. Hamilton-Nelson; Wei Gu; Cristina Razquin; Pau Pastor; Ignacio Mateo; Michael J. Owen; Kelley M. Faber; Palmi V. Jonsson; Onofre Combarros; Michael C. O'Donovan; Laura B. Cantwell; Hilkka Soininen; Deborah Blacker; Simon Mead; Thomas H. Mosley; David A. Bennett; Tamara B. Harris; Laura Fratiglioni; Clive Holmes; Renee F.A.G. De Bruijn; Peter Passmore; Thomas J. Montine; Karolien Bettens; Jerome I. Rotter; Alexis Brice; Kevin Morgan; Tatiana M. Foroud; Walter A. Kukull; Didier Hannequin; John F. Powell; Michael A. Nalls; Karen Ritchie; Kathryn L. Lunetta; John S.K. Kauwe; Eric Boerwinkle; Matthias Riemenschneider; Mercè Boada; Mikko Hiltunen; Eden R. Martin; Reinhold Schmidt; Dan Rujescu; Jean François Dartigues; Richard Mayeux; Christophe Tzourio; Albert Hofman; Markus M. Nöthen; Caroline Graff; Bruce M. Psaty; Jonathan L. Haines; Mark Lathrop; Margaret A. Pericak-Vance; Lenore J. Launer; Christine Van Broeckhoven; Lindsay A. Farrer; Cornelia M. Van Duijn; Alfredo Ramirez; Sudha Seshadri; Gerard D. Schellenberg; Philippe Amouyel; Julie Williams

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, Vilmundur Gudnason, Carlos Cruchaga, David Craig, Najaf Amin, Claudine Berr, Oscar L. Lopez, Philip L. De Jager, Vincent Deramecourt, Janet A. Johnston, Denis Evans, Simon Lovestone, Luc Letenneur, Isabel Hernández, David C. Rubinsztein, Gudny Eiriksdottir, Kristel Sleegers, Alison M. Goate, Nathalie Fiévet, Matthew J. Huentelman, Michael Gill, Kristelle Brown, M. Ilyas Kamboh, Lina Keller, Pascale Barberger-Gateau, Bernadette McGuinness, Eric B. Larson, Amanda J. Myers, Carole Dufouil, Stephen Todd, David Wallon, Seth Love, Ekaterina Rogaeva, John Gallacher, Peter St George-Hyslop, Jordi Clarimon, Alberto Lleo, Anthony Bayer, Debby W. Tsuang, Lei Yu, Magda Tsolaki, Paola Bossù, Gianfranco Spalletta, Petra Proitsi, John Collinge, Sandro Sorbi, Florentino Sanchez Garcia, Nick C. Fox, John Hardy, Maria Candida Deniz Naranjo, Paolo Bosco, Robert Clarke, Carol Brayne, Daniela Galimberti, Elio Scarpini, Ubaldo Bonuccelli, Michelangelo Mancuso, Gabriele Siciliano, Susanne Moebus, Patrizia Mecocci, Maria Del Zompo, Wolfgang Maier, Harald Hampel, Alberto Pilotto, Ana Frank-García, Francesco Panza, Vincenzo Solfrizzi, Paolo Caffarra, Benedetta Nacmias, William Perry, Manuel Mayhaus, Lars Lannfelt, Hakon Hakonarson, Sabrina Pichler, Minerva M. Carrasquillo, Martin Ingelsson, Duane Beekly, Victoria Alvarez, Fanggeng Zou, Otto Valladares, Steven G. Younkin, Eliecer Coto, Kara L. Hamilton-Nelson, Wei Gu, Cristina Razquin, Pau Pastor, Ignacio Mateo, Michael J. Owen, Kelley M. Faber, Palmi V. Jonsson, Onofre Combarros, Michael C. O'Donovan, Laura B. Cantwell, Hilkka Soininen, Deborah Blacker, Simon Mead, Thomas H. Mosley, David A. Bennett, Tamara B. Harris, Laura Fratiglioni, Clive Holmes, Renee F.A.G. De Bruijn, Peter Passmore, Thomas J. Montine, Karolien Bettens, Jerome I. Rotter, Alexis Brice, Kevin Morgan, Tatiana M. Foroud, Walter A. Kukull, Didier Hannequin, John F. Powell, Michael A. Nalls, Karen Ritchie, Kathryn L. Lunetta, John S.K. Kauwe, Eric Boerwinkle, Matthias Riemenschneider, Mercè Boada, Mikko Hiltunen, Eden R. Martin, Reinhold Schmidt, Dan Rujescu, Jean François Dartigues, Richard Mayeux, Christophe Tzourio, Albert Hofman, Markus M. Nöthen, Caroline Graff, Bruce M. Psaty, Jonathan L. Haines, Mark Lathrop, Margaret A. Pericak-Vance, Lenore J. Launer, Christine Van Broeckhoven, Lindsay A. Farrer, Cornelia M. Van Duijn, Alfredo Ramirez, Sudha Seshadri, Gerard D. Schellenberg, Philippe Amouyel, Julie Williams

Neuroscience

Research output: Contribution to journal › Article › peer-review

70 Scopus citations

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 (US)
Article number	e94661
Journal	PloS one
Volume	9
Issue number	6
DOIs	https://doi.org/10.1371/journal.pone.0094661
State	Published - Jun 12 2014

ASJC Scopus subject areas

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10.1371/journal.pone.0094661

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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., ... Williams, J. (2014). Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease. PloS one, 9(6), Article e94661. https://doi.org/10.1371/journal.pone.0094661

Escott-Price, V, Bellenguez, C, Wang, LS, Choi, SH, Harold, D, Jones, L, Holmans, P, Gerrish, A, Vedernikov, A, Richards, A, DeStefano, AL, Lambert, JC, 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, Arfan Ikram, M, Zelenika, D, Vardarajan, BN, Kamatani, Y, Lin, CF, Schmidt, H, Kunkle, B, Dunstan, ML, Vronskaya, M, Johnson, AD, Ruiz, A, Bihoreau, MT, Reitz, C, Pasquier, F, Hollingworth, P, Hanon, O, Fitzpatrick, AL, Buxbaum, JD, Campion, D, Crane, PK, Becker, CBT, Gudnason, V, Cruchaga, C, Craig, D, Amin, N, Berr, C, Lopez, OL, De Jager, PL, Deramecourt, V, Johnston, JA, Evans, D, Lovestone, S, Letenneur, L, Hernández, I, Rubinsztein, DC, Eiriksdottir, G, Sleegers, K, Goate, AM, Fiévet, N, Huentelman, MJ, Gill, M, Brown, K, Kamboh, MI, Keller, L, Barberger-Gateau, P, McGuinness, B, Larson, EB, Myers, AJ, Dufouil, C, Todd, S, Wallon, D, Love, S, Rogaeva, E, Gallacher, J, St George-Hyslop, P, Clarimon, J, Lleo, A, Bayer, A, Tsuang, DW, Yu, L, Tsolaki, M, Bossù, P, Spalletta, G, Proitsi, P, Collinge, J, Sorbi, S, Sanchez Garcia, F, Fox, NC, Hardy, J, Naranjo, MCD, Bosco, P, Clarke, R, Brayne, C, Galimberti, D, Scarpini, E, Bonuccelli, U, Mancuso, M, Siciliano, G, Moebus, S, Mecocci, P, Del Zompo, M, Maier, W, Hampel, H, Pilotto, A, Frank-García, A, Panza, F, Solfrizzi, V, Caffarra, P, Nacmias, B, Perry, W, Mayhaus, M, Lannfelt, L, Hakonarson, H, Pichler, S, Carrasquillo, MM, Ingelsson, M, Beekly, D, Alvarez, V, Zou, F, Valladares, O, Younkin, SG, Coto, E, Hamilton-Nelson, KL, Gu, W, Razquin, C, Pastor, P, Mateo, I, Owen, MJ, Faber, KM, Jonsson, PV, Combarros, O, O'Donovan, MC, Cantwell, LB, Soininen, H, Blacker, D, Mead, S, Mosley, TH, Bennett, DA, Harris, TB, Fratiglioni, L, Holmes, C, De Bruijn, RFAG, Passmore, P, Montine, TJ, Bettens, K, Rotter, JI, Brice, A, Morgan, K, Foroud, TM, Kukull, WA, Hannequin, D, Powell, JF, Nalls, MA, Ritchie, K, Lunetta, KL, Kauwe, JSK, Boerwinkle, E, Riemenschneider, M, Boada, M, Hiltunen, M, Martin, ER, Schmidt, R, Rujescu, D, Dartigues, JF, Mayeux, R, Tzourio, C, Hofman, A, Nöthen, MM, Graff, C, Psaty, BM, Haines, JL, Lathrop, M, Pericak-Vance, MA, Launer, LJ, Van Broeckhoven, C, Farrer, LA, Van Duijn, CM, Ramirez, A, Seshadri, S, Schellenberg, GD, Amouyel, P & Williams, J 2014, 'Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease', PloS one, vol. 9, no. 6, e94661. https://doi.org/10.1371/journal.pone.0094661

@article{c38bc0d506144e08ba6258793a16f5c3,

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 Wang, {Li San} and Choi, {Seung Hoan} and Denise Harold and Lesley Jones and Peter Holmans and Amy Gerrish and Alexey Vedernikov and Alexander Richards and DeStefano, {Anita L.} and Lambert, {Jean Charles} 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 {Arfan Ikram}, M. and Diana Zelenika and Vardarajan, {Badri N.} and Yoichiro Kamatani and Lin, {Chiao Feng} and Helena Schmidt and Brian Kunkle and Dunstan, {Melanie L.} and Maria Vronskaya and Johnson, {Andrew D.} and Agustin Ruiz and Bihoreau, {Marie Th{\'e}r{\`e}se} 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 Becker, {Clinton Baldwin Tim} and Vilmundur Gudnason and Carlos Cruchaga and David Craig and Najaf Amin and Claudine Berr and Lopez, {Oscar L.} and {De Jager}, {Philip L.} and Vincent Deramecourt and Johnston, {Janet A.} and Denis Evans and Simon Lovestone and Luc Letenneur and Isabel Hern{\'a}ndez and Rubinsztein, {David C.} and Gudny Eiriksdottir and Kristel Sleegers and Goate, {Alison M.} and Nathalie Fi{\'e}vet and Huentelman, {Matthew J.} and Michael Gill and Kristelle Brown and Kamboh, {M. Ilyas} and Lina Keller and Pascale Barberger-Gateau and Bernadette McGuinness and Larson, {Eric B.} and Myers, {Amanda J.} and Carole Dufouil and Stephen Todd and David Wallon and Seth Love and Ekaterina Rogaeva and John Gallacher and {St George-Hyslop}, Peter and Jordi Clarimon and Alberto Lleo and Anthony Bayer and Tsuang, {Debby W.} and Lei Yu and Magda Tsolaki and Paola Boss{\`u} and Gianfranco Spalletta and Petra Proitsi and John Collinge and Sandro Sorbi and {Sanchez Garcia}, Florentino and Fox, {Nick C.} and John Hardy and Naranjo, {Maria Candida Deniz} and Paolo Bosco and Robert Clarke and Carol Brayne and Daniela Galimberti and Elio Scarpini and Ubaldo Bonuccelli and Michelangelo Mancuso and Gabriele Siciliano and Susanne Moebus and Patrizia Mecocci and {Del Zompo}, Maria and Wolfgang Maier and Harald Hampel and Alberto Pilotto and Ana Frank-Garc{\'i}a and Francesco Panza and Vincenzo Solfrizzi and Paolo Caffarra and Benedetta Nacmias and William Perry and Manuel Mayhaus and Lars Lannfelt and Hakon Hakonarson and Sabrina Pichler and Carrasquillo, {Minerva M.} and Martin Ingelsson and Duane Beekly and Victoria Alvarez and Fanggeng Zou and Otto Valladares and Younkin, {Steven G.} and Eliecer Coto and Hamilton-Nelson, {Kara L.} and Wei Gu and Cristina Razquin and Pau Pastor and Ignacio Mateo and Owen, {Michael J.} and Faber, {Kelley M.} and Jonsson, {Palmi V.} and Onofre Combarros and O'Donovan, {Michael C.} and Cantwell, {Laura B.} and Hilkka Soininen and Deborah Blacker and Simon Mead and Mosley, {Thomas H.} and Bennett, {David A.} and Harris, {Tamara B.} and Laura Fratiglioni and Clive Holmes and {De Bruijn}, {Renee F.A.G.} and Peter Passmore and Montine, {Thomas J.} and Karolien Bettens and Rotter, {Jerome I.} and Alexis Brice and Kevin Morgan and Foroud, {Tatiana M.} and Kukull, {Walter A.} and Didier Hannequin and Powell, {John F.} and Nalls, {Michael A.} and Karen Ritchie and Lunetta, {Kathryn L.} and Kauwe, {John S.K.} and Eric Boerwinkle and Matthias Riemenschneider and Merc{\`e} Boada and Mikko Hiltunen and Martin, {Eden R.} and Reinhold Schmidt and Dan Rujescu and Dartigues, {Jean Fran{\c c}ois} and Richard Mayeux and Christophe Tzourio and Albert Hofman and N{\"o}then, {Markus M.} and Caroline Graff and Psaty, {Bruce M.} and Haines, {Jonathan L.} and Mark Lathrop and Pericak-Vance, {Margaret A.} and Launer, {Lenore J.} and {Van Broeckhoven}, Christine and Farrer, {Lindsay A.} and {Van Duijn}, {Cornelia M.} and Alfredo Ramirez and Sudha Seshadri and Schellenberg, {Gerard D.} and Philippe Amouyel and Julie Williams",

year = "2014",

month = jun,

day = "12",

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

language = "English (US)",

volume = "9",

journal = "PloS one",

issn = "1932-6203",

publisher = "Public Library of Science",

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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 - Arfan Ikram, M.

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 - Becker, Clinton Baldwin Tim

AU - Gudnason, Vilmundur

AU - Cruchaga, Carlos

AU - Craig, David

AU - Amin, Najaf

AU - Berr, Claudine

AU - Lopez, Oscar L.

AU - De Jager, Philip L.

AU - Deramecourt, Vincent

AU - Johnston, Janet A.

AU - Evans, Denis

AU - Lovestone, Simon

AU - Letenneur, Luc

AU - Hernández, Isabel

AU - Rubinsztein, David C.

AU - Eiriksdottir, Gudny

AU - Sleegers, Kristel

AU - Goate, Alison M.

AU - Fiévet, Nathalie

AU - Huentelman, Matthew J.

AU - Gill, Michael

AU - Brown, Kristelle

AU - Kamboh, M. Ilyas

AU - Keller, Lina

AU - Barberger-Gateau, Pascale

AU - McGuinness, Bernadette

AU - Larson, Eric B.

AU - Myers, Amanda J.

AU - Dufouil, Carole

AU - Todd, Stephen

AU - Wallon, David

AU - Love, Seth

AU - Rogaeva, Ekaterina

AU - Gallacher, John

AU - St George-Hyslop, Peter

AU - Clarimon, Jordi

AU - Lleo, Alberto

AU - Bayer, Anthony

AU - Tsuang, Debby W.

AU - Yu, Lei

AU - Tsolaki, Magda

AU - Bossù, Paola

AU - Spalletta, Gianfranco

AU - Proitsi, Petra

AU - Collinge, John

AU - Sorbi, Sandro

AU - Sanchez Garcia, Florentino

AU - Fox, Nick C.

AU - Hardy, John

AU - Naranjo, Maria Candida Deniz

AU - Bosco, Paolo

AU - Clarke, Robert

AU - Brayne, Carol

AU - Galimberti, Daniela

AU - Scarpini, Elio

AU - Bonuccelli, Ubaldo

AU - Mancuso, Michelangelo

AU - Siciliano, Gabriele

AU - Moebus, Susanne

AU - Mecocci, Patrizia

AU - Del Zompo, Maria

AU - Maier, Wolfgang

AU - Hampel, Harald

AU - Pilotto, Alberto

AU - Frank-García, Ana

AU - Panza, Francesco

AU - Solfrizzi, Vincenzo

AU - Caffarra, Paolo

AU - Nacmias, Benedetta

AU - Perry, William

AU - Mayhaus, Manuel

AU - Lannfelt, Lars

AU - Hakonarson, Hakon

AU - Pichler, Sabrina

AU - Carrasquillo, Minerva M.

AU - Ingelsson, Martin

AU - Beekly, Duane

AU - Alvarez, Victoria

AU - Zou, Fanggeng

AU - Valladares, Otto

AU - Younkin, Steven G.

AU - Coto, Eliecer

AU - Hamilton-Nelson, Kara L.

AU - Gu, Wei

AU - Razquin, Cristina

AU - Pastor, Pau

AU - Mateo, Ignacio

AU - Owen, Michael J.

AU - Faber, Kelley M.

AU - Jonsson, Palmi V.

AU - Combarros, Onofre

AU - O'Donovan, Michael C.

AU - Cantwell, Laura B.

AU - Soininen, Hilkka

AU - Blacker, Deborah

AU - Mead, Simon

AU - Mosley, Thomas H.

AU - Bennett, David A.

AU - Harris, Tamara B.

AU - Fratiglioni, Laura

AU - Holmes, Clive

AU - De Bruijn, Renee F.A.G.

AU - Passmore, Peter

AU - Montine, Thomas J.

AU - Bettens, Karolien

AU - Rotter, Jerome I.

AU - Brice, Alexis

AU - Morgan, Kevin

AU - Foroud, Tatiana M.

AU - Kukull, Walter A.

AU - Hannequin, Didier

AU - Powell, John F.

AU - Nalls, Michael A.

AU - Ritchie, Karen

AU - Lunetta, Kathryn L.

AU - Kauwe, John S.K.

AU - Boerwinkle, Eric

AU - Riemenschneider, Matthias

AU - Boada, Mercè

AU - Hiltunen, Mikko

AU - Martin, Eden R.

AU - Schmidt, Reinhold

AU - Rujescu, Dan

AU - Dartigues, Jean François

AU - Mayeux, Richard

AU - Tzourio, Christophe

AU - Hofman, Albert

AU - Nöthen, Markus M.

AU - Graff, Caroline

AU - Psaty, Bruce M.

AU - Haines, Jonathan L.

AU - Lathrop, Mark

AU - Pericak-Vance, Margaret A.

AU - Launer, Lenore J.

AU - Van Broeckhoven, Christine

AU - Farrer, Lindsay A.

AU - Van Duijn, Cornelia M.

AU - Ramirez, Alfredo

AU - Seshadri, Sudha

AU - Schellenberg, Gerard D.

AU - Amouyel, Philippe

AU - Williams, Julie

PY - 2014/6/12

Y1 - 2014/6/12

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.

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U2 - 10.1371/journal.pone.0094661

DO - 10.1371/journal.pone.0094661

M3 - Article

C2 - 24922517

AN - SCOPUS:84903520463

SN - 1932-6203

VL - 9

JO - PloS one

JF - PloS one

IS - 6

M1 - e94661

ER -

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

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