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

Escott-Price, V and Bellenguez, C and Wang, LS and Choi, SH and Harold, D and Jones, L and Holmans, P and Gerrish, A and Vedernikov, A and Richards, A and DeStefano, AL and Lambert, JC and Ibrahim-Verbaas, CA and Naj, AC and Sims, R and Jun, G and Bis, JC and Beecham, GW and Grenier-Boley, B and Russo, G and Thornton-Wells, TA and Denning, N and Smith, AV and Chouraki, V and Thomas, C and Arfan Ikram, M and Zelenika, D and Vardarajan, BN and Kamatani, Y and Lin, CF and Schmidt, H and Kunkle, B and Dunstan, ML and Vronskaya, M and Johnson, AD and Ruiz, A and Bihoreau, MT and Reitz, C and Pasquier, F and Hollingworth, P and Hanon, O and Fitzpatrick, AL and Buxbaum, JD and Campion, D and Crane, PK and Becker, CBT and Gudnason, V and Cruchaga, C and Craig, D and Amin, N and Berr, C and Lopez, OL and De Jager, PL and Deramecourt, V and Johnston, JA and Evans, D and Lovestone, S and Letenneur, L and Hernández, I and Rubinsztein, DC and Eiriksdottir, G and Sleegers, K and Goate, AM and Fiévet, N and Huentelman, MJ and Gill, M and Brown, K and Kamboh, MI and Keller, L and Barberger-Gateau, P and McGuinness, B and Larson, EB and Myers, AJ and Dufouil, C and Todd, S and Wallon, D and Love, S and Rogaeva, E and Gallacher, J and St George-Hyslop, P and Clarimon, J and Lleo, A and Bayer, A and Tsuang, DW and Yu, L and Tsolaki, M and Bossù, P and Spalletta, G and Proitsi, P and Collinge, J and Sorbi, S and Sanchez Garcia, F and Fox, NC and Hardy, J and Naranjo, MCD and Bosco, P and Clarke, R and Brayne, C and Galimberti, D and Scarpini, E (2014) Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease. PLoS ONE, 9 (6).

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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.


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Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
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, OLollopez@pitt.eduOLLOPEZ
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, MIkamboh@pitt.eduKAMBOH
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
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorYao, Yong-GangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Centers: Other Centers, Institutes, Offices, or Units > Alzheimer's Disease Research Center
Date: 12 June 2014
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 9
Number: 6
DOI or Unique Handle: 10.1371/journal.pone.0094661
Schools and Programs: Graduate School of Public Health > Human Genetics
School of Medicine > Neurology
Refereed: Yes
Date Deposited: 25 Jun 2014 15:31
Last Modified: 22 Jun 2021 13:55
URI: http://d-scholarship.pitt.edu/id/eprint/22108

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