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Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease, and shows evidence for additional susceptibility genes
We undertook a two-stage genome-wide association study of Alzheimer's disease involving over 16,000 individuals. In stage 1 (3,941 cases and 7,848 controls), we replicated the established association with the APOE locus (most significant SNP: rs2075650, p= 1.8×10(−157)) and observed genome-wide...
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| Formato: | Texto |
| Lenguaje: | English |
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2009
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| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2845877/ https://www.ncbi.nlm.nih.gov/pubmed/19734902 http://dx.doi.org/10.1038/ng.440 |
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| author | Harold, Denise Abraham, Richard Hollingworth, Paul Sims, Rebecca Gerrish, Amy Hamshere, Marian Singh Pahwa, Jaspreet Moskvina, Valentina Dowzell, Kimberley Williams, Amy Jones, Nicola Thomas, Charlene Stretton, Alexandra Morgan, Angharad Lovestone, Simon Powell, John Proitsi, Petroula Lupton, Michelle K Brayne, Carol Rubinsztein, David C. Gill, Michael Lawlor, Brian Lynch, Aoibhinn Morgan, Kevin Brown, Kristelle Passmore, Peter Craig, David McGuinness, Bernadette Todd, Stephen Holmes, Clive Mann, David Smith, A. David Love, Seth Kehoe, Patrick G. Hardy, John Mead, Simon Fox, Nick Rossor, Martin Collinge, John Maier, Wolfgang Jessen, Frank Schürmann, Britta van den Bussche, Hendrik Heuser, Isabella Kornhuber, Johannes Wiltfang, Jens Dichgans, Martin Frölich, Lutz Hampel, Harald Hüll, Michael Rujescu, Dan Goate, Alison Kauwe, John S.K. Cruchaga, Carlos Nowotny, Petra Morris, John C. Mayo, Kevin Sleegers, Kristel Bettens, Karolien Engelborghs, Sebastiaan De Deyn, Peter van Broeckhoven, Christine Livingston, Gill Bass, Nicholas J. Gurling, Hugh McQuillin, Andrew Gwilliam, Rhian Deloukas, Panagiotis Al-Chalabi, Ammar Shaw, Christopher E. Tsolaki, Magda Singleton, Andrew Guerreiro, Rita Mühleisen, Thomas W. Nöthen, Markus M. Moebus, Susanne Jöckel, Karl-Heinz Klopp, Norman Wichmann, H-Erich Carrasquillo, Minerva M. Pankratz, V. Shane Younkin, Steven G. Holmans, Peter O'Donovan, Michael Owen, Michael J. Williams, Julie |
| author_facet | Harold, Denise Abraham, Richard Hollingworth, Paul Sims, Rebecca Gerrish, Amy Hamshere, Marian Singh Pahwa, Jaspreet Moskvina, Valentina Dowzell, Kimberley Williams, Amy Jones, Nicola Thomas, Charlene Stretton, Alexandra Morgan, Angharad Lovestone, Simon Powell, John Proitsi, Petroula Lupton, Michelle K Brayne, Carol Rubinsztein, David C. Gill, Michael Lawlor, Brian Lynch, Aoibhinn Morgan, Kevin Brown, Kristelle Passmore, Peter Craig, David McGuinness, Bernadette Todd, Stephen Holmes, Clive Mann, David Smith, A. David Love, Seth Kehoe, Patrick G. Hardy, John Mead, Simon Fox, Nick Rossor, Martin Collinge, John Maier, Wolfgang Jessen, Frank Schürmann, Britta van den Bussche, Hendrik Heuser, Isabella Kornhuber, Johannes Wiltfang, Jens Dichgans, Martin Frölich, Lutz Hampel, Harald Hüll, Michael Rujescu, Dan Goate, Alison Kauwe, John S.K. Cruchaga, Carlos Nowotny, Petra Morris, John C. Mayo, Kevin Sleegers, Kristel Bettens, Karolien Engelborghs, Sebastiaan De Deyn, Peter van Broeckhoven, Christine Livingston, Gill Bass, Nicholas J. Gurling, Hugh McQuillin, Andrew Gwilliam, Rhian Deloukas, Panagiotis Al-Chalabi, Ammar Shaw, Christopher E. Tsolaki, Magda Singleton, Andrew Guerreiro, Rita Mühleisen, Thomas W. Nöthen, Markus M. Moebus, Susanne Jöckel, Karl-Heinz Klopp, Norman Wichmann, H-Erich Carrasquillo, Minerva M. Pankratz, V. Shane Younkin, Steven G. Holmans, Peter O'Donovan, Michael Owen, Michael J. Williams, Julie |
| author_sort | Harold, Denise |
| collection | PubMed |
| description | We undertook a two-stage genome-wide association study of Alzheimer's disease involving over 16,000 individuals. In stage 1 (3,941 cases and 7,848 controls), we replicated the established association with the APOE locus (most significant SNP: rs2075650, p= 1.8×10(−157)) and observed genome-wide significant association with SNPs at two novel loci: rs11136000 in the CLU or APOJ gene (p= 1.4×10(−9)) and rs3851179, a SNP 5′ to the PICALM gene (p= 1.9×10(−8)). Both novel associations were supported in stage 2 (2,023 cases and 2,340 controls), producing compelling evidence for association with AD in the combined dataset (rs11136000: p= 8.5×10(−10), odds ratio= 0.86; rs3851179: p= 1.3×10(−9), odds ratio= 0.86). We also observed more variants associated at p< 1×10(−5) than expected by chance (p=7.5×10(−6)), including polymorphisms at the BIN1, DAB1 and CR1 loci. |
| format | Text |
| id | pubmed-2845877 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2009 |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-28458772010-04-01 Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease, and shows evidence for additional susceptibility genes Harold, Denise Abraham, Richard Hollingworth, Paul Sims, Rebecca Gerrish, Amy Hamshere, Marian Singh Pahwa, Jaspreet Moskvina, Valentina Dowzell, Kimberley Williams, Amy Jones, Nicola Thomas, Charlene Stretton, Alexandra Morgan, Angharad Lovestone, Simon Powell, John Proitsi, Petroula Lupton, Michelle K Brayne, Carol Rubinsztein, David C. Gill, Michael Lawlor, Brian Lynch, Aoibhinn Morgan, Kevin Brown, Kristelle Passmore, Peter Craig, David McGuinness, Bernadette Todd, Stephen Holmes, Clive Mann, David Smith, A. David Love, Seth Kehoe, Patrick G. Hardy, John Mead, Simon Fox, Nick Rossor, Martin Collinge, John Maier, Wolfgang Jessen, Frank Schürmann, Britta van den Bussche, Hendrik Heuser, Isabella Kornhuber, Johannes Wiltfang, Jens Dichgans, Martin Frölich, Lutz Hampel, Harald Hüll, Michael Rujescu, Dan Goate, Alison Kauwe, John S.K. Cruchaga, Carlos Nowotny, Petra Morris, John C. Mayo, Kevin Sleegers, Kristel Bettens, Karolien Engelborghs, Sebastiaan De Deyn, Peter van Broeckhoven, Christine Livingston, Gill Bass, Nicholas J. Gurling, Hugh McQuillin, Andrew Gwilliam, Rhian Deloukas, Panagiotis Al-Chalabi, Ammar Shaw, Christopher E. Tsolaki, Magda Singleton, Andrew Guerreiro, Rita Mühleisen, Thomas W. Nöthen, Markus M. Moebus, Susanne Jöckel, Karl-Heinz Klopp, Norman Wichmann, H-Erich Carrasquillo, Minerva M. Pankratz, V. Shane Younkin, Steven G. Holmans, Peter O'Donovan, Michael Owen, Michael J. Williams, Julie Nat Genet Article We undertook a two-stage genome-wide association study of Alzheimer's disease involving over 16,000 individuals. In stage 1 (3,941 cases and 7,848 controls), we replicated the established association with the APOE locus (most significant SNP: rs2075650, p= 1.8×10(−157)) and observed genome-wide significant association with SNPs at two novel loci: rs11136000 in the CLU or APOJ gene (p= 1.4×10(−9)) and rs3851179, a SNP 5′ to the PICALM gene (p= 1.9×10(−8)). Both novel associations were supported in stage 2 (2,023 cases and 2,340 controls), producing compelling evidence for association with AD in the combined dataset (rs11136000: p= 8.5×10(−10), odds ratio= 0.86; rs3851179: p= 1.3×10(−9), odds ratio= 0.86). We also observed more variants associated at p< 1×10(−5) than expected by chance (p=7.5×10(−6)), including polymorphisms at the BIN1, DAB1 and CR1 loci. 2009-09-06 2009-10 /pmc/articles/PMC2845877/ /pubmed/19734902 http://dx.doi.org/10.1038/ng.440 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
| spellingShingle | Article Harold, Denise Abraham, Richard Hollingworth, Paul Sims, Rebecca Gerrish, Amy Hamshere, Marian Singh Pahwa, Jaspreet Moskvina, Valentina Dowzell, Kimberley Williams, Amy Jones, Nicola Thomas, Charlene Stretton, Alexandra Morgan, Angharad Lovestone, Simon Powell, John Proitsi, Petroula Lupton, Michelle K Brayne, Carol Rubinsztein, David C. Gill, Michael Lawlor, Brian Lynch, Aoibhinn Morgan, Kevin Brown, Kristelle Passmore, Peter Craig, David McGuinness, Bernadette Todd, Stephen Holmes, Clive Mann, David Smith, A. David Love, Seth Kehoe, Patrick G. Hardy, John Mead, Simon Fox, Nick Rossor, Martin Collinge, John Maier, Wolfgang Jessen, Frank Schürmann, Britta van den Bussche, Hendrik Heuser, Isabella Kornhuber, Johannes Wiltfang, Jens Dichgans, Martin Frölich, Lutz Hampel, Harald Hüll, Michael Rujescu, Dan Goate, Alison Kauwe, John S.K. Cruchaga, Carlos Nowotny, Petra Morris, John C. Mayo, Kevin Sleegers, Kristel Bettens, Karolien Engelborghs, Sebastiaan De Deyn, Peter van Broeckhoven, Christine Livingston, Gill Bass, Nicholas J. Gurling, Hugh McQuillin, Andrew Gwilliam, Rhian Deloukas, Panagiotis Al-Chalabi, Ammar Shaw, Christopher E. Tsolaki, Magda Singleton, Andrew Guerreiro, Rita Mühleisen, Thomas W. Nöthen, Markus M. Moebus, Susanne Jöckel, Karl-Heinz Klopp, Norman Wichmann, H-Erich Carrasquillo, Minerva M. Pankratz, V. Shane Younkin, Steven G. Holmans, Peter O'Donovan, Michael Owen, Michael J. Williams, Julie Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease, and shows evidence for additional susceptibility genes |
| title | Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease, and shows evidence for additional susceptibility genes |
| title_full | Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease, and shows evidence for additional susceptibility genes |
| title_fullStr | Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease, and shows evidence for additional susceptibility genes |
| title_full_unstemmed | Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease, and shows evidence for additional susceptibility genes |
| title_short | Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease, and shows evidence for additional susceptibility genes |
| title_sort | genome-wide association study identifies variants at clu and picalm associated with alzheimer's disease, and shows evidence for additional susceptibility genes |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2845877/ https://www.ncbi.nlm.nih.gov/pubmed/19734902 http://dx.doi.org/10.1038/ng.440 |
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