Common variants at 12q14 and 12q24 are associated with hippocampal volume

Aging is associated with reductions in hippocampal volume (HV) that are accelerated by Alzheimer’s disease and vascular risk factors. Our genome-wide association study of dementia-free persons (n=9,232) identified 46 SNPs at four loci with p-values <4.0×10-7. Two additional samples (n=2,318) repl...

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Main Authors:	Bis, Joshua C., DeCarli, Charles, Smith, Albert Vernon, van der Lijn, Fedde, Crivello, Fabrice, Fornage, Myriam, Debette, Stephanie, Shulman, Joshua M., Schmidt, Helena, Srikanth, Velandai, Schuur, Maaike, Yu, Lei, Choi, Seung-Hoan, Sigurdsson, Sigurdur, Verhaaren, Benjamin F.J., DeStefano, Anita L., Lambert, Jean-Charles, Jack, Clifford R., Struchalin, Maksim, Stankovich, Jim, Ibrahim-Verbaas, Carla A., Fleischman, Debra, Zijdenbos, Alex, den Heijer, Tom, Mazoyer, Bernard, Coker, Laura H., Enzinger, Christian, Danoy, Patrick, Amin, Najaf, Arfanakis, Konstantinos, van Buchem, Mark A., de Bruijn, Renée F.A.G., Beiser, Alexa, Dufouil, Carole, Huang, Juebin, Cavalieri, Margherita, Thomson, Russell, Niessen, Wiro J., Chibnik, Lori B., Gislason, Gauti K., Hofman, Albert, Pikula, Aleksandra, Amouyel, Philippe, Freeman, Kevin B., Phan, Thanh G., Oostra, Ben A., Stein, Jason L., Medland, Sarah E., Vasquez, Alejandro Arias, Hibar, Derrek P., Wright, Margaret J., Franke, Barbara, Martin, Nicholas G., Thompson, Paul M., Nalls, Michael A., Uitterlinden, Andre G., Au, Rhoda, Elbaz, Alexis, Beare, Richard J., van Swieten, John C., Lopez, Oscar, Harris, Tamara B., Chouraki, Vincent, Breteler, Monique M.B., De Jager, Philip L., Becker, James T., Vernooij, Meike W., Knopman, David, Fazekas, Franz, Wolf, Philip A., van der Lugt, Aad, Gudnason, Vilmundur, Longstreth, W.T., Brown, Mathew A., Bennett, David A., van Duijn, Cornelia M., Mosley, Thomas H., Schmidt, Reinhold, Tzourio, Christophe, Launer, Lenore J., Ikram, M. Arfan, Seshadri, Sudha
Format:	Online
Language:	English
Published:	2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3427729/

id	pubmed-3427729
recordtype	oai_dc
spelling	pubmed-34277292012-11-01 Common variants at 12q14 and 12q24 are associated with hippocampal volume Bis, Joshua C. DeCarli, Charles Smith, Albert Vernon van der Lijn, Fedde Crivello, Fabrice Fornage, Myriam Debette, Stephanie Shulman, Joshua M. Schmidt, Helena Srikanth, Velandai Schuur, Maaike Yu, Lei Choi, Seung-Hoan Sigurdsson, Sigurdur Verhaaren, Benjamin F.J. DeStefano, Anita L. Lambert, Jean-Charles Jack, Clifford R. Struchalin, Maksim Stankovich, Jim Ibrahim-Verbaas, Carla A. Fleischman, Debra Zijdenbos, Alex den Heijer, Tom Mazoyer, Bernard Coker, Laura H. Enzinger, Christian Danoy, Patrick Amin, Najaf Arfanakis, Konstantinos van Buchem, Mark A. de Bruijn, Renée F.A.G. Beiser, Alexa Dufouil, Carole Huang, Juebin Cavalieri, Margherita Thomson, Russell Niessen, Wiro J. Chibnik, Lori B. Gislason, Gauti K. Hofman, Albert Pikula, Aleksandra Amouyel, Philippe Freeman, Kevin B. Phan, Thanh G. Oostra, Ben A. Stein, Jason L. Medland, Sarah E. Vasquez, Alejandro Arias Hibar, Derrek P. Wright, Margaret J. Franke, Barbara Martin, Nicholas G. Thompson, Paul M. Nalls, Michael A. Uitterlinden, Andre G. Au, Rhoda Elbaz, Alexis Beare, Richard J. van Swieten, John C. Lopez, Oscar Harris, Tamara B. Chouraki, Vincent Breteler, Monique M.B. De Jager, Philip L. Becker, James T. Vernooij, Meike W. Knopman, David Fazekas, Franz Wolf, Philip A. van der Lugt, Aad Gudnason, Vilmundur Longstreth, W.T. Brown, Mathew A. Bennett, David A. van Duijn, Cornelia M. Mosley, Thomas H. Schmidt, Reinhold Tzourio, Christophe Launer, Lenore J. Ikram, M. Arfan Seshadri, Sudha Article Aging is associated with reductions in hippocampal volume (HV) that are accelerated by Alzheimer’s disease and vascular risk factors. Our genome-wide association study of dementia-free persons (n=9,232) identified 46 SNPs at four loci with p-values <4.0×10-7. Two additional samples (n=2,318) replicated associations at 12q24 within MSRB3/WIF1 (discovery + replication, rs17178006; p=5.3×10-11) and at 12q14 near HRK/FBXW8 (rs7294919; p=2.9×10-11). Remaining associations included one 2q24 SNP within DPP4 (rs6741949; p=2.9×10-7) and nine 9p33 SNPs within ASTN2 (rs7852872; p=1.0×10-7) that were also associated with HV (p<0.05) in a third younger, more heterogeneous sample (n=7,794). The ASTN2 SNP was also associated with decline in cognition in a largely independent sample (n=1,563). These associations implicate genes related to apoptosis (HRK), development (WIF1), oxidative stress (MSR3B), ubiquitination (FBXW8), enzymes targeted by new diabetes medications (DPP4), and neuronal migration (ASTN2), indicating novel genetic influences that influence hippocampal size and possibly the risk of cognitive decline and dementia. 2012-04-15 /pmc/articles/PMC3427729/ /pubmed/22504421 http://dx.doi.org/10.1038/ng.2237 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download 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
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Bis, Joshua C. DeCarli, Charles Smith, Albert Vernon van der Lijn, Fedde Crivello, Fabrice Fornage, Myriam Debette, Stephanie Shulman, Joshua M. Schmidt, Helena Srikanth, Velandai Schuur, Maaike Yu, Lei Choi, Seung-Hoan Sigurdsson, Sigurdur Verhaaren, Benjamin F.J. DeStefano, Anita L. Lambert, Jean-Charles Jack, Clifford R. Struchalin, Maksim Stankovich, Jim Ibrahim-Verbaas, Carla A. Fleischman, Debra Zijdenbos, Alex den Heijer, Tom Mazoyer, Bernard Coker, Laura H. Enzinger, Christian Danoy, Patrick Amin, Najaf Arfanakis, Konstantinos van Buchem, Mark A. de Bruijn, Renée F.A.G. Beiser, Alexa Dufouil, Carole Huang, Juebin Cavalieri, Margherita Thomson, Russell Niessen, Wiro J. Chibnik, Lori B. Gislason, Gauti K. Hofman, Albert Pikula, Aleksandra Amouyel, Philippe Freeman, Kevin B. Phan, Thanh G. Oostra, Ben A. Stein, Jason L. Medland, Sarah E. Vasquez, Alejandro Arias Hibar, Derrek P. Wright, Margaret J. Franke, Barbara Martin, Nicholas G. Thompson, Paul M. Nalls, Michael A. Uitterlinden, Andre G. Au, Rhoda Elbaz, Alexis Beare, Richard J. van Swieten, John C. Lopez, Oscar Harris, Tamara B. Chouraki, Vincent Breteler, Monique M.B. De Jager, Philip L. Becker, James T. Vernooij, Meike W. Knopman, David Fazekas, Franz Wolf, Philip A. van der Lugt, Aad Gudnason, Vilmundur Longstreth, W.T. Brown, Mathew A. Bennett, David A. van Duijn, Cornelia M. Mosley, Thomas H. Schmidt, Reinhold Tzourio, Christophe Launer, Lenore J. Ikram, M. Arfan Seshadri, Sudha
spellingShingle	Bis, Joshua C. DeCarli, Charles Smith, Albert Vernon van der Lijn, Fedde Crivello, Fabrice Fornage, Myriam Debette, Stephanie Shulman, Joshua M. Schmidt, Helena Srikanth, Velandai Schuur, Maaike Yu, Lei Choi, Seung-Hoan Sigurdsson, Sigurdur Verhaaren, Benjamin F.J. DeStefano, Anita L. Lambert, Jean-Charles Jack, Clifford R. Struchalin, Maksim Stankovich, Jim Ibrahim-Verbaas, Carla A. Fleischman, Debra Zijdenbos, Alex den Heijer, Tom Mazoyer, Bernard Coker, Laura H. Enzinger, Christian Danoy, Patrick Amin, Najaf Arfanakis, Konstantinos van Buchem, Mark A. de Bruijn, Renée F.A.G. Beiser, Alexa Dufouil, Carole Huang, Juebin Cavalieri, Margherita Thomson, Russell Niessen, Wiro J. Chibnik, Lori B. Gislason, Gauti K. Hofman, Albert Pikula, Aleksandra Amouyel, Philippe Freeman, Kevin B. Phan, Thanh G. Oostra, Ben A. Stein, Jason L. Medland, Sarah E. Vasquez, Alejandro Arias Hibar, Derrek P. Wright, Margaret J. Franke, Barbara Martin, Nicholas G. Thompson, Paul M. Nalls, Michael A. Uitterlinden, Andre G. Au, Rhoda Elbaz, Alexis Beare, Richard J. van Swieten, John C. Lopez, Oscar Harris, Tamara B. Chouraki, Vincent Breteler, Monique M.B. De Jager, Philip L. Becker, James T. Vernooij, Meike W. Knopman, David Fazekas, Franz Wolf, Philip A. van der Lugt, Aad Gudnason, Vilmundur Longstreth, W.T. Brown, Mathew A. Bennett, David A. van Duijn, Cornelia M. Mosley, Thomas H. Schmidt, Reinhold Tzourio, Christophe Launer, Lenore J. Ikram, M. Arfan Seshadri, Sudha Common variants at 12q14 and 12q24 are associated with hippocampal volume
author_facet	Bis, Joshua C. DeCarli, Charles Smith, Albert Vernon van der Lijn, Fedde Crivello, Fabrice Fornage, Myriam Debette, Stephanie Shulman, Joshua M. Schmidt, Helena Srikanth, Velandai Schuur, Maaike Yu, Lei Choi, Seung-Hoan Sigurdsson, Sigurdur Verhaaren, Benjamin F.J. DeStefano, Anita L. Lambert, Jean-Charles Jack, Clifford R. Struchalin, Maksim Stankovich, Jim Ibrahim-Verbaas, Carla A. Fleischman, Debra Zijdenbos, Alex den Heijer, Tom Mazoyer, Bernard Coker, Laura H. Enzinger, Christian Danoy, Patrick Amin, Najaf Arfanakis, Konstantinos van Buchem, Mark A. de Bruijn, Renée F.A.G. Beiser, Alexa Dufouil, Carole Huang, Juebin Cavalieri, Margherita Thomson, Russell Niessen, Wiro J. Chibnik, Lori B. Gislason, Gauti K. Hofman, Albert Pikula, Aleksandra Amouyel, Philippe Freeman, Kevin B. Phan, Thanh G. Oostra, Ben A. Stein, Jason L. Medland, Sarah E. Vasquez, Alejandro Arias Hibar, Derrek P. Wright, Margaret J. Franke, Barbara Martin, Nicholas G. Thompson, Paul M. Nalls, Michael A. Uitterlinden, Andre G. Au, Rhoda Elbaz, Alexis Beare, Richard J. van Swieten, John C. Lopez, Oscar Harris, Tamara B. Chouraki, Vincent Breteler, Monique M.B. De Jager, Philip L. Becker, James T. Vernooij, Meike W. Knopman, David Fazekas, Franz Wolf, Philip A. van der Lugt, Aad Gudnason, Vilmundur Longstreth, W.T. Brown, Mathew A. Bennett, David A. van Duijn, Cornelia M. Mosley, Thomas H. Schmidt, Reinhold Tzourio, Christophe Launer, Lenore J. Ikram, M. Arfan Seshadri, Sudha
author_sort	Bis, Joshua C.
title	Common variants at 12q14 and 12q24 are associated with hippocampal volume
title_short	Common variants at 12q14 and 12q24 are associated with hippocampal volume
title_full	Common variants at 12q14 and 12q24 are associated with hippocampal volume
title_fullStr	Common variants at 12q14 and 12q24 are associated with hippocampal volume
title_full_unstemmed	Common variants at 12q14 and 12q24 are associated with hippocampal volume
title_sort	common variants at 12q14 and 12q24 are associated with hippocampal volume
description	Aging is associated with reductions in hippocampal volume (HV) that are accelerated by Alzheimer’s disease and vascular risk factors. Our genome-wide association study of dementia-free persons (n=9,232) identified 46 SNPs at four loci with p-values <4.0×10-7. Two additional samples (n=2,318) replicated associations at 12q24 within MSRB3/WIF1 (discovery + replication, rs17178006; p=5.3×10-11) and at 12q14 near HRK/FBXW8 (rs7294919; p=2.9×10-11). Remaining associations included one 2q24 SNP within DPP4 (rs6741949; p=2.9×10-7) and nine 9p33 SNPs within ASTN2 (rs7852872; p=1.0×10-7) that were also associated with HV (p<0.05) in a third younger, more heterogeneous sample (n=7,794). The ASTN2 SNP was also associated with decline in cognition in a largely independent sample (n=1,563). These associations implicate genes related to apoptosis (HRK), development (WIF1), oxidative stress (MSR3B), ubiquitination (FBXW8), enzymes targeted by new diabetes medications (DPP4), and neuronal migration (ASTN2), indicating novel genetic influences that influence hippocampal size and possibly the risk of cognitive decline and dementia.
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3427729/
_version_	1611552228944904192

Common variants at 12q14 and 12q24 are associated with hippocampal volume

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