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Gene-based analysis in HRC imputed genome wide association data identifies three novel genes for Alzheimer’s disease

Late onset Alzheimer’s disease is the most common form of dementia for which about 30 susceptibility loci have been reported. The aim of the current study is to identify novel genes associated with Alzheimer’s disease using the largest up-to-date reference single nucleotide polymorphism (SNP) panel,...

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Autores principales: Baker, Emily, Sims, Rebecca, Leonenko, Ganna, Frizzati, Aura, Harwood, Janet C., Grozeva, Detelina, Morgan, Kevin, Passmore, Peter, Holmes, Clive, Powell, John, Brayne, Carol, Gill, Michael, Mead, Simon, Bossù, Paola, Spalletta, Gianfranco, Goate, Alison M., Cruchaga, Carlos, Maier, Wolfgang, Heun, Reinhard, Jessen, Frank, Peters, Oliver, Dichgans, Martin, FröLich, Lutz, Ramirez, Alfredo, Jones, Lesley, Hardy, John, Ivanov, Dobril, Hill, Matthew, Holmans, Peter, Allen, Nicholas D., Morgan, B. Paul, Seshadri, Sudha, Schellenberg, Gerard D., Amouyel, Philippe, Williams, Julie, Escott-Price, Valentina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6613773/
https://www.ncbi.nlm.nih.gov/pubmed/31283791
http://dx.doi.org/10.1371/journal.pone.0218111
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author Baker, Emily
Sims, Rebecca
Leonenko, Ganna
Frizzati, Aura
Harwood, Janet C.
Grozeva, Detelina
Morgan, Kevin
Passmore, Peter
Holmes, Clive
Powell, John
Brayne, Carol
Gill, Michael
Mead, Simon
Bossù, Paola
Spalletta, Gianfranco
Goate, Alison M.
Cruchaga, Carlos
Maier, Wolfgang
Heun, Reinhard
Jessen, Frank
Peters, Oliver
Dichgans, Martin
FröLich, Lutz
Ramirez, Alfredo
Jones, Lesley
Hardy, John
Ivanov, Dobril
Hill, Matthew
Holmans, Peter
Allen, Nicholas D.
Morgan, B. Paul
Seshadri, Sudha
Schellenberg, Gerard D.
Amouyel, Philippe
Williams, Julie
Escott-Price, Valentina
author_facet Baker, Emily
Sims, Rebecca
Leonenko, Ganna
Frizzati, Aura
Harwood, Janet C.
Grozeva, Detelina
Morgan, Kevin
Passmore, Peter
Holmes, Clive
Powell, John
Brayne, Carol
Gill, Michael
Mead, Simon
Bossù, Paola
Spalletta, Gianfranco
Goate, Alison M.
Cruchaga, Carlos
Maier, Wolfgang
Heun, Reinhard
Jessen, Frank
Peters, Oliver
Dichgans, Martin
FröLich, Lutz
Ramirez, Alfredo
Jones, Lesley
Hardy, John
Ivanov, Dobril
Hill, Matthew
Holmans, Peter
Allen, Nicholas D.
Morgan, B. Paul
Seshadri, Sudha
Schellenberg, Gerard D.
Amouyel, Philippe
Williams, Julie
Escott-Price, Valentina
author_sort Baker, Emily
collection PubMed
description Late onset Alzheimer’s disease is the most common form of dementia for which about 30 susceptibility loci have been reported. The aim of the current study is to identify novel genes associated with Alzheimer’s disease using the largest up-to-date reference single nucleotide polymorphism (SNP) panel, the most accurate imputation software and a novel gene-based analysis 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 million genotypes from 17,008 Alzheimer’s cases and 37,154 controls. In addition to earlier reported genes, we detected three novel gene-wide significant loci PPARGC1A (p = 2.2 × 10(−6)), RORA (p = 7.4 × 10(−7)) and ZNF423 (p = 2.1 × 10(−6)). PPARGC1A and RORA are involved in circadian rhythm; circadian disturbances are one of the earliest symptoms of Alzheimer’s disease. PPARGC1A is additionally linked to energy metabolism and the generation of amyloid beta plaques. RORA is involved in a variety of functions apart from circadian rhythm, such as cholesterol metabolism and inflammation. The ZNF423 gene resides in an Alzheimer’s disease-specific protein network and is likely involved with centrosomes and DNA damage repair.
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spelling pubmed-66137732019-07-23 Gene-based analysis in HRC imputed genome wide association data identifies three novel genes for Alzheimer’s disease Baker, Emily Sims, Rebecca Leonenko, Ganna Frizzati, Aura Harwood, Janet C. Grozeva, Detelina Morgan, Kevin Passmore, Peter Holmes, Clive Powell, John Brayne, Carol Gill, Michael Mead, Simon Bossù, Paola Spalletta, Gianfranco Goate, Alison M. Cruchaga, Carlos Maier, Wolfgang Heun, Reinhard Jessen, Frank Peters, Oliver Dichgans, Martin FröLich, Lutz Ramirez, Alfredo Jones, Lesley Hardy, John Ivanov, Dobril Hill, Matthew Holmans, Peter Allen, Nicholas D. Morgan, B. Paul Seshadri, Sudha Schellenberg, Gerard D. Amouyel, Philippe Williams, Julie Escott-Price, Valentina PLoS One Research Article Late onset Alzheimer’s disease is the most common form of dementia for which about 30 susceptibility loci have been reported. The aim of the current study is to identify novel genes associated with Alzheimer’s disease using the largest up-to-date reference single nucleotide polymorphism (SNP) panel, the most accurate imputation software and a novel gene-based analysis 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 million genotypes from 17,008 Alzheimer’s cases and 37,154 controls. In addition to earlier reported genes, we detected three novel gene-wide significant loci PPARGC1A (p = 2.2 × 10(−6)), RORA (p = 7.4 × 10(−7)) and ZNF423 (p = 2.1 × 10(−6)). PPARGC1A and RORA are involved in circadian rhythm; circadian disturbances are one of the earliest symptoms of Alzheimer’s disease. PPARGC1A is additionally linked to energy metabolism and the generation of amyloid beta plaques. RORA is involved in a variety of functions apart from circadian rhythm, such as cholesterol metabolism and inflammation. The ZNF423 gene resides in an Alzheimer’s disease-specific protein network and is likely involved with centrosomes and DNA damage repair. Public Library of Science 2019-07-08 /pmc/articles/PMC6613773/ /pubmed/31283791 http://dx.doi.org/10.1371/journal.pone.0218111 Text en © 2019 Baker et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Baker, Emily
Sims, Rebecca
Leonenko, Ganna
Frizzati, Aura
Harwood, Janet C.
Grozeva, Detelina
Morgan, Kevin
Passmore, Peter
Holmes, Clive
Powell, John
Brayne, Carol
Gill, Michael
Mead, Simon
Bossù, Paola
Spalletta, Gianfranco
Goate, Alison M.
Cruchaga, Carlos
Maier, Wolfgang
Heun, Reinhard
Jessen, Frank
Peters, Oliver
Dichgans, Martin
FröLich, Lutz
Ramirez, Alfredo
Jones, Lesley
Hardy, John
Ivanov, Dobril
Hill, Matthew
Holmans, Peter
Allen, Nicholas D.
Morgan, B. Paul
Seshadri, Sudha
Schellenberg, Gerard D.
Amouyel, Philippe
Williams, Julie
Escott-Price, Valentina
Gene-based analysis in HRC imputed genome wide association data identifies three novel genes for Alzheimer’s disease
title Gene-based analysis in HRC imputed genome wide association data identifies three novel genes for Alzheimer’s disease
title_full Gene-based analysis in HRC imputed genome wide association data identifies three novel genes for Alzheimer’s disease
title_fullStr Gene-based analysis in HRC imputed genome wide association data identifies three novel genes for Alzheimer’s disease
title_full_unstemmed Gene-based analysis in HRC imputed genome wide association data identifies three novel genes for Alzheimer’s disease
title_short Gene-based analysis in HRC imputed genome wide association data identifies three novel genes for Alzheimer’s disease
title_sort gene-based analysis in hrc imputed genome wide association data identifies three novel genes for alzheimer’s disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6613773/
https://www.ncbi.nlm.nih.gov/pubmed/31283791
http://dx.doi.org/10.1371/journal.pone.0218111
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