Identification of common variants associated with human hippocampal and intracranial volumes

Identifying genetic variants influencing human brain structures may reveal new biological mechanisms underlying cognition and neuropsychiatric illness. The volume of the hippocampus is a biomarker of incipient Alzheimer's disease and is reduced in schizophrenia, major depression and mesial temp...

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Main Authors:	Stein, J., Medland, S., Vasquez, A., Hibar, D., Senstad, R., Winkler, A., Toro, R., Appel, K., Bartecek, R., Bergmann, O., Bernard, M., Brown, A., Cannon, D., Chakravarty, M., Christoforou, A., Domin, M., Grimm, O., Hollinshead, M., Holmes, A., Homuth, G., Hottenga, J., Langan, C., Lopez, L., Hansell, N., Hwang, K., Kim, S., Laje, G., Lee, P., Liu, X., Loth, E., Lourdusamy, A., Mattingsdal, M., Mohnke, S., Maniega, S., Nho, K., Nugent, A., O'Brien, C., Papmeyer, M., Putz, B., Ramasamy, A., Rasmussen, J., Rijpkema, M., Risacher, S., Roddey, J., Rose, E., Ryten, M., Shen, L., Sprooten, E., Strengman, E., Teumer, A., Trabzuni, D., Turner, J., van Eijk, K., van Erp, T., van Tol, M., Wittfeld, K., Wolf, C., Woudstra, S., Aleman, A., Alhusaini, S., Almasy, L., Binder, E., Brohawn, D., Cantor, R., Carless, M., Corvin, A., Czisch, M., Curran, J., Davies, G., de Almeida, M., Delanty, N., Depondt, C., Duggirala, R., Dyer, T., Erk, S., Fagerness, J., Fox, P., Freimer, N., Gill, M., Goering, H., Hagler, D., Hoehn, D., Holsboer, F., Hoogman, M., Hosten, N., Jahanshad, N., Johnson, M., Kasperaviciute, D., Kent, J., Kochunov, P., Lancaster, J., Lawrie, S., Liewald, D., Mandl, R., Matarin, M., Mattheisen, M., Meisenzahl, E., Melle, I., Moses, Eric, Muehleisen, T., Nauck, M., Noethen, M., Olvera, R., Pandolfo, M., Pike, G., Puls, R., Reinvang, I., Renteria, M., Rietschel, M., Roffman, J., Royle, N., Rujescu, D., Savitz, J., Schnack, H., Schnell, K., Seiferth, N., Smith, C., Steen, V., Hernandez, M., Van den Heuvel, M., van der Wee, N., Van Haren, N., Veltman, J., Voelzke, H., Walker, R., Westlye, L., Whelan, C., Agartz, I., Boomsma, D., Cavalleri, G., Dale, A., Djurovic, S., Drevets, W., Hagoort, P., Hall, J., Heinz, A., Jack, C., Foroud, T., Le Hellard, S., Macciardi, F., Montgomery, G., Poline, J., Porteous, D., Sisodiya, S., Starr, J., Sussmann, J., Toga, A., Veltman, D., Walter, H., Weiner, M., Bis, J., Ikram, M., Smith, A., Gudnason, V., Tzourio, C., Vernooij, M., Launer, L., DeCarli, C., Seshadri, S., Andreassen, O., Apostolova, L., Bastin, M., Blangero, J., Brunner, H., Buckner, R., Cichon, S., Coppola, G., de Zubicaray, G., Deary, I., Donohoe, G., de Geus, E., Espeseth, T., Fernandez, G., Glahn, D., Grabe, H., Hardy, J., Pol, H., Jenkinson, M., Kahn, R., McDonald, C., McIntosh, A., McMahon, F., McMahon, K., Meyer-Lindenberg, A., Morris, D., Mueller-Myhsok, B., Nichols, T., Ophoff, R., Paus, T., Pausova, Z., Penninx, B., Potkin, S., Saemann, P., Saykin, A., Schumann, G., Smoller, J., Wardlaw, J., Weale, M., Martin, N., Franke, B., Wright, M., Thompson, P.
Format:	Journal Article
Published:	Nature Publishing Group 2012
Online Access:	http://hdl.handle.net/20.500.11937/66466

_version_	1848761328313827328
author	Stein, J. Medland, S. Vasquez, A. Hibar, D. Senstad, R. Winkler, A. Toro, R. Appel, K. Bartecek, R. Bergmann, O. Bernard, M. Brown, A. Cannon, D. Chakravarty, M. Christoforou, A. Domin, M. Grimm, O. Hollinshead, M. Holmes, A. Homuth, G. Hottenga, J. Langan, C. Lopez, L. Hansell, N. Hwang, K. Kim, S. Laje, G. Lee, P. Liu, X. Loth, E. Lourdusamy, A. Mattingsdal, M. Mohnke, S. Maniega, S. Nho, K. Nugent, A. O'Brien, C. Papmeyer, M. Putz, B. Ramasamy, A. Rasmussen, J. Rijpkema, M. Risacher, S. Roddey, J. Rose, E. Ryten, M. Shen, L. Sprooten, E. Strengman, E. Teumer, A. Trabzuni, D. Turner, J. van Eijk, K. van Erp, T. van Tol, M. Wittfeld, K. Wolf, C. Woudstra, S. Aleman, A. Alhusaini, S. Almasy, L. Binder, E. Brohawn, D. Cantor, R. Carless, M. Corvin, A. Czisch, M. Curran, J. Davies, G. de Almeida, M. Delanty, N. Depondt, C. Duggirala, R. Dyer, T. Erk, S. Fagerness, J. Fox, P. Freimer, N. Gill, M. Goering, H. Hagler, D. Hoehn, D. Holsboer, F. Hoogman, M. Hosten, N. Jahanshad, N. Johnson, M. Kasperaviciute, D. Kent, J. Kochunov, P. Lancaster, J. Lawrie, S. Liewald, D. Mandl, R. Matarin, M. Mattheisen, M. Meisenzahl, E. Melle, I. Moses, Eric Muehleisen, T. Nauck, M. Noethen, M. Olvera, R. Pandolfo, M. Pike, G. Puls, R. Reinvang, I. Renteria, M. Rietschel, M. Roffman, J. Royle, N. Rujescu, D. Savitz, J. Schnack, H. Schnell, K. Seiferth, N. Smith, C. Steen, V. Hernandez, M. Van den Heuvel, M. van der Wee, N. Van Haren, N. Veltman, J. Voelzke, H. Walker, R. Westlye, L. Whelan, C. Agartz, I. Boomsma, D. Cavalleri, G. Dale, A. Djurovic, S. Drevets, W. Hagoort, P. Hall, J. Heinz, A. Jack, C. Foroud, T. Le Hellard, S. Macciardi, F. Montgomery, G. Poline, J. Porteous, D. Sisodiya, S. Starr, J. Sussmann, J. Toga, A. Veltman, D. Walter, H. Weiner, M. Bis, J. Ikram, M. Smith, A. Gudnason, V. Tzourio, C. Vernooij, M. Launer, L. DeCarli, C. Seshadri, S. Andreassen, O. Apostolova, L. Bastin, M. Blangero, J. Brunner, H. Buckner, R. Cichon, S. Coppola, G. de Zubicaray, G. Deary, I. Donohoe, G. de Geus, E. Espeseth, T. Fernandez, G. Glahn, D. Grabe, H. Hardy, J. Pol, H. Jenkinson, M. Kahn, R. McDonald, C. McIntosh, A. McMahon, F. McMahon, K. Meyer-Lindenberg, A. Morris, D. Mueller-Myhsok, B. Nichols, T. Ophoff, R. Paus, T. Pausova, Z. Penninx, B. Potkin, S. Saemann, P. Saykin, A. Schumann, G. Smoller, J. Wardlaw, J. Weale, M. Martin, N. Franke, B. Wright, M. Thompson, P.
author_facet	Stein, J. Medland, S. Vasquez, A. Hibar, D. Senstad, R. Winkler, A. Toro, R. Appel, K. Bartecek, R. Bergmann, O. Bernard, M. Brown, A. Cannon, D. Chakravarty, M. Christoforou, A. Domin, M. Grimm, O. Hollinshead, M. Holmes, A. Homuth, G. Hottenga, J. Langan, C. Lopez, L. Hansell, N. Hwang, K. Kim, S. Laje, G. Lee, P. Liu, X. Loth, E. Lourdusamy, A. Mattingsdal, M. Mohnke, S. Maniega, S. Nho, K. Nugent, A. O'Brien, C. Papmeyer, M. Putz, B. Ramasamy, A. Rasmussen, J. Rijpkema, M. Risacher, S. Roddey, J. Rose, E. Ryten, M. Shen, L. Sprooten, E. Strengman, E. Teumer, A. Trabzuni, D. Turner, J. van Eijk, K. van Erp, T. van Tol, M. Wittfeld, K. Wolf, C. Woudstra, S. Aleman, A. Alhusaini, S. Almasy, L. Binder, E. Brohawn, D. Cantor, R. Carless, M. Corvin, A. Czisch, M. Curran, J. Davies, G. de Almeida, M. Delanty, N. Depondt, C. Duggirala, R. Dyer, T. Erk, S. Fagerness, J. Fox, P. Freimer, N. Gill, M. Goering, H. Hagler, D. Hoehn, D. Holsboer, F. Hoogman, M. Hosten, N. Jahanshad, N. Johnson, M. Kasperaviciute, D. Kent, J. Kochunov, P. Lancaster, J. Lawrie, S. Liewald, D. Mandl, R. Matarin, M. Mattheisen, M. Meisenzahl, E. Melle, I. Moses, Eric Muehleisen, T. Nauck, M. Noethen, M. Olvera, R. Pandolfo, M. Pike, G. Puls, R. Reinvang, I. Renteria, M. Rietschel, M. Roffman, J. Royle, N. Rujescu, D. Savitz, J. Schnack, H. Schnell, K. Seiferth, N. Smith, C. Steen, V. Hernandez, M. Van den Heuvel, M. van der Wee, N. Van Haren, N. Veltman, J. Voelzke, H. Walker, R. Westlye, L. Whelan, C. Agartz, I. Boomsma, D. Cavalleri, G. Dale, A. Djurovic, S. Drevets, W. Hagoort, P. Hall, J. Heinz, A. Jack, C. Foroud, T. Le Hellard, S. Macciardi, F. Montgomery, G. Poline, J. Porteous, D. Sisodiya, S. Starr, J. Sussmann, J. Toga, A. Veltman, D. Walter, H. Weiner, M. Bis, J. Ikram, M. Smith, A. Gudnason, V. Tzourio, C. Vernooij, M. Launer, L. DeCarli, C. Seshadri, S. Andreassen, O. Apostolova, L. Bastin, M. Blangero, J. Brunner, H. Buckner, R. Cichon, S. Coppola, G. de Zubicaray, G. Deary, I. Donohoe, G. de Geus, E. Espeseth, T. Fernandez, G. Glahn, D. Grabe, H. Hardy, J. Pol, H. Jenkinson, M. Kahn, R. McDonald, C. McIntosh, A. McMahon, F. McMahon, K. Meyer-Lindenberg, A. Morris, D. Mueller-Myhsok, B. Nichols, T. Ophoff, R. Paus, T. Pausova, Z. Penninx, B. Potkin, S. Saemann, P. Saykin, A. Schumann, G. Smoller, J. Wardlaw, J. Weale, M. Martin, N. Franke, B. Wright, M. Thompson, P.
author_sort	Stein, J.
building	Curtin Institutional Repository
collection	Online Access
description	Identifying genetic variants influencing human brain structures may reveal new biological mechanisms underlying cognition and neuropsychiatric illness. The volume of the hippocampus is a biomarker of incipient Alzheimer's disease and is reduced in schizophrenia, major depression and mesial temporal lobe epilepsy. Whereas many brain imaging phenotypes are highly heritable, identifying and replicating genetic influences has been difficult, as small effects and the high costs of magnetic resonance imaging (MRI) have led to underpowered studies. Here we report genome-wide association meta-analyses and replication for mean bilateral hippocampal, total brain and intracranial volumes from a large multinational consortium. The intergenic variant rs7294919 was associated with hippocampal volume (12q24.22; N = 21,151; P = 6.70 Ã— 10 -16) and the expression levels of the positional candidate gene TESC in brain tissue. Additionally, rs10784502, located within HMGA2, was associated with intracranial volume (12q14.3; N = 15,782; P = 1.12 Ã— 10 -12). We also identified a suggestive association with total brain volume at rs10494373 within DDR2 (1q23.3; N = 6,500; P = 5.81 Ã— 10 -7). Â© 2012 Nature America, Inc. All rights reserved.
first_indexed	2025-11-14T10:29:55Z
format	Journal Article
id	curtin-20.500.11937-66466
institution	Curtin University Malaysia
institution_category	Local University
last_indexed	2025-11-14T10:29:55Z
publishDate	2012
publisher	Nature Publishing Group
recordtype	eprints
repository_type	Digital Repository
spelling	curtin-20.500.11937-664662018-04-30T02:49:05Z Identification of common variants associated with human hippocampal and intracranial volumes Stein, J. Medland, S. Vasquez, A. Hibar, D. Senstad, R. Winkler, A. Toro, R. Appel, K. Bartecek, R. Bergmann, O. Bernard, M. Brown, A. Cannon, D. Chakravarty, M. Christoforou, A. Domin, M. Grimm, O. Hollinshead, M. Holmes, A. Homuth, G. Hottenga, J. Langan, C. Lopez, L. Hansell, N. Hwang, K. Kim, S. Laje, G. Lee, P. Liu, X. Loth, E. Lourdusamy, A. Mattingsdal, M. Mohnke, S. Maniega, S. Nho, K. Nugent, A. O'Brien, C. Papmeyer, M. Putz, B. Ramasamy, A. Rasmussen, J. Rijpkema, M. Risacher, S. Roddey, J. Rose, E. Ryten, M. Shen, L. Sprooten, E. Strengman, E. Teumer, A. Trabzuni, D. Turner, J. van Eijk, K. van Erp, T. van Tol, M. Wittfeld, K. Wolf, C. Woudstra, S. Aleman, A. Alhusaini, S. Almasy, L. Binder, E. Brohawn, D. Cantor, R. Carless, M. Corvin, A. Czisch, M. Curran, J. Davies, G. de Almeida, M. Delanty, N. Depondt, C. Duggirala, R. Dyer, T. Erk, S. Fagerness, J. Fox, P. Freimer, N. Gill, M. Goering, H. Hagler, D. Hoehn, D. Holsboer, F. Hoogman, M. Hosten, N. Jahanshad, N. Johnson, M. Kasperaviciute, D. Kent, J. Kochunov, P. Lancaster, J. Lawrie, S. Liewald, D. Mandl, R. Matarin, M. Mattheisen, M. Meisenzahl, E. Melle, I. Moses, Eric Muehleisen, T. Nauck, M. Noethen, M. Olvera, R. Pandolfo, M. Pike, G. Puls, R. Reinvang, I. Renteria, M. Rietschel, M. Roffman, J. Royle, N. Rujescu, D. Savitz, J. Schnack, H. Schnell, K. Seiferth, N. Smith, C. Steen, V. Hernandez, M. Van den Heuvel, M. van der Wee, N. Van Haren, N. Veltman, J. Voelzke, H. Walker, R. Westlye, L. Whelan, C. Agartz, I. Boomsma, D. Cavalleri, G. Dale, A. Djurovic, S. Drevets, W. Hagoort, P. Hall, J. Heinz, A. Jack, C. Foroud, T. Le Hellard, S. Macciardi, F. Montgomery, G. Poline, J. Porteous, D. Sisodiya, S. Starr, J. Sussmann, J. Toga, A. Veltman, D. Walter, H. Weiner, M. Bis, J. Ikram, M. Smith, A. Gudnason, V. Tzourio, C. Vernooij, M. Launer, L. DeCarli, C. Seshadri, S. Andreassen, O. Apostolova, L. Bastin, M. Blangero, J. Brunner, H. Buckner, R. Cichon, S. Coppola, G. de Zubicaray, G. Deary, I. Donohoe, G. de Geus, E. Espeseth, T. Fernandez, G. Glahn, D. Grabe, H. Hardy, J. Pol, H. Jenkinson, M. Kahn, R. McDonald, C. McIntosh, A. McMahon, F. McMahon, K. Meyer-Lindenberg, A. Morris, D. Mueller-Myhsok, B. Nichols, T. Ophoff, R. Paus, T. Pausova, Z. Penninx, B. Potkin, S. Saemann, P. Saykin, A. Schumann, G. Smoller, J. Wardlaw, J. Weale, M. Martin, N. Franke, B. Wright, M. Thompson, P. Identifying genetic variants influencing human brain structures may reveal new biological mechanisms underlying cognition and neuropsychiatric illness. The volume of the hippocampus is a biomarker of incipient Alzheimer's disease and is reduced in schizophrenia, major depression and mesial temporal lobe epilepsy. Whereas many brain imaging phenotypes are highly heritable, identifying and replicating genetic influences has been difficult, as small effects and the high costs of magnetic resonance imaging (MRI) have led to underpowered studies. Here we report genome-wide association meta-analyses and replication for mean bilateral hippocampal, total brain and intracranial volumes from a large multinational consortium. The intergenic variant rs7294919 was associated with hippocampal volume (12q24.22; N = 21,151; P = 6.70 Ã— 10 -16) and the expression levels of the positional candidate gene TESC in brain tissue. Additionally, rs10784502, located within HMGA2, was associated with intracranial volume (12q14.3; N = 15,782; P = 1.12 Ã— 10 -12). We also identified a suggestive association with total brain volume at rs10494373 within DDR2 (1q23.3; N = 6,500; P = 5.81 Ã— 10 -7). Â© 2012 Nature America, Inc. All rights reserved. 2012 Journal Article http://hdl.handle.net/20.500.11937/66466 10.1038/ng.2250 Nature Publishing Group restricted
spellingShingle	Stein, J. Medland, S. Vasquez, A. Hibar, D. Senstad, R. Winkler, A. Toro, R. Appel, K. Bartecek, R. Bergmann, O. Bernard, M. Brown, A. Cannon, D. Chakravarty, M. Christoforou, A. Domin, M. Grimm, O. Hollinshead, M. Holmes, A. Homuth, G. Hottenga, J. Langan, C. Lopez, L. Hansell, N. Hwang, K. Kim, S. Laje, G. Lee, P. Liu, X. Loth, E. Lourdusamy, A. Mattingsdal, M. Mohnke, S. Maniega, S. Nho, K. Nugent, A. O'Brien, C. Papmeyer, M. Putz, B. Ramasamy, A. Rasmussen, J. Rijpkema, M. Risacher, S. Roddey, J. Rose, E. Ryten, M. Shen, L. Sprooten, E. Strengman, E. Teumer, A. Trabzuni, D. Turner, J. van Eijk, K. van Erp, T. van Tol, M. Wittfeld, K. Wolf, C. Woudstra, S. Aleman, A. Alhusaini, S. Almasy, L. Binder, E. Brohawn, D. Cantor, R. Carless, M. Corvin, A. Czisch, M. Curran, J. Davies, G. de Almeida, M. Delanty, N. Depondt, C. Duggirala, R. Dyer, T. Erk, S. Fagerness, J. Fox, P. Freimer, N. Gill, M. Goering, H. Hagler, D. Hoehn, D. Holsboer, F. Hoogman, M. Hosten, N. Jahanshad, N. Johnson, M. Kasperaviciute, D. Kent, J. Kochunov, P. Lancaster, J. Lawrie, S. Liewald, D. Mandl, R. Matarin, M. Mattheisen, M. Meisenzahl, E. Melle, I. Moses, Eric Muehleisen, T. Nauck, M. Noethen, M. Olvera, R. Pandolfo, M. Pike, G. Puls, R. Reinvang, I. Renteria, M. Rietschel, M. Roffman, J. Royle, N. Rujescu, D. Savitz, J. Schnack, H. Schnell, K. Seiferth, N. Smith, C. Steen, V. Hernandez, M. Van den Heuvel, M. van der Wee, N. Van Haren, N. Veltman, J. Voelzke, H. Walker, R. Westlye, L. Whelan, C. Agartz, I. Boomsma, D. Cavalleri, G. Dale, A. Djurovic, S. Drevets, W. Hagoort, P. Hall, J. Heinz, A. Jack, C. Foroud, T. Le Hellard, S. Macciardi, F. Montgomery, G. Poline, J. Porteous, D. Sisodiya, S. Starr, J. Sussmann, J. Toga, A. Veltman, D. Walter, H. Weiner, M. Bis, J. Ikram, M. Smith, A. Gudnason, V. Tzourio, C. Vernooij, M. Launer, L. DeCarli, C. Seshadri, S. Andreassen, O. Apostolova, L. Bastin, M. Blangero, J. Brunner, H. Buckner, R. Cichon, S. Coppola, G. de Zubicaray, G. Deary, I. Donohoe, G. de Geus, E. Espeseth, T. Fernandez, G. Glahn, D. Grabe, H. Hardy, J. Pol, H. Jenkinson, M. Kahn, R. McDonald, C. McIntosh, A. McMahon, F. McMahon, K. Meyer-Lindenberg, A. Morris, D. Mueller-Myhsok, B. Nichols, T. Ophoff, R. Paus, T. Pausova, Z. Penninx, B. Potkin, S. Saemann, P. Saykin, A. Schumann, G. Smoller, J. Wardlaw, J. Weale, M. Martin, N. Franke, B. Wright, M. Thompson, P. Identification of common variants associated with human hippocampal and intracranial volumes
title	Identification of common variants associated with human hippocampal and intracranial volumes
title_full	Identification of common variants associated with human hippocampal and intracranial volumes
title_fullStr	Identification of common variants associated with human hippocampal and intracranial volumes
title_full_unstemmed	Identification of common variants associated with human hippocampal and intracranial volumes
title_short	Identification of common variants associated with human hippocampal and intracranial volumes
title_sort	identification of common variants associated with human hippocampal and intracranial volumes
url	http://hdl.handle.net/20.500.11937/66466

Identification of common variants associated with human hippocampal and intracranial volumes

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