Identification of common variants associated with human hippocampal and intracranial volumes

Jason L. Stein, Sarah E. Medland, Alejandro Arias Vasquez, Derrek P. Hibar, Rudy E. Senstad, Anderson M. Winkler, Roberto Toro, Katja Appel, Richard Bartecek, Ørjan Bergmann, Manon Bernard, Andrew A. Brown, Dara M. Cannon, M. Mallar Chakravarty, Andrea Christoforou, Martin Domin, Oliver Grimm, Marisa Hollinshead, Avram J. Holmes, Georg Homuth & 182 others Jouke Jan Hottenga, Camilla Langan, Lorna M. Lopez, Narelle K. Hansell, Kristy S. Hwang, Sungeun Kim, Gonzalo Laje, Phil H. Lee, Xinmin Liu, Eva Loth, Anbarasu Lourdusamy, Morten Mattingsdal, Sebastian Mohnke, Susana Muñoz Maniega, Kwangsik Nho, Allison C. Nugent, Carol O'brien, Martina Papmeyer, Benno Pütz, Adaikalavan Ramasamy, Jerod Rasmussen, Mark Rijpkema, Shannon L. Risacher, J. Cooper Roddey, Emma J. Rose, Mina Ryten, Li Shen, Emma Sprooten, Eric Strengman, Alexander Teumer, Daniah Trabzuni, Jessica Turner, Kristel Van Eijk, Theo G M Van Erp, Marie Jose Van Tol, Katharina Wittfeld, Christiane Wolf, Saskia Woudstra, Andre Aleman, Saud Alhusaini, Laura Almasy, Elisabeth B. Binder, David G. Brohawn, Rita M. Cantor, Melanie A. Carless, Aiden Corvin, Michael Czisch, Joanne E. Curran, Gail Davies, Marcio A A De Almeida, Norman Delanty, Chantal Depondt, Ravi Duggirala, Thomas D. Dyer, Susanne Erk, Jesen Fagerness, Peter T. Fox, Nelson B. Freimer, Michael Gill, Harald H H Göring, Donald J. Hagler, David Hoehn, Florian Holsboer, Martine Hoogman, Norbert Hosten, Neda Jahanshad, Matthew P. Johnson, Dalia Kasperaviciute, Jack W. Kent, Peter Kochunov, Jack L. Lancaster, Stephen M. Lawrie, David C. Liewald, René Mandl, Mar Matarin, Manuel Mattheisen, Eva Meisenzahl, Ingrid Melle, Eric K. Moses, Thomas W. Mühleisen, Matthias Nauck, Markus M. Nöthen, Rene L. Olvera, Massimo Pandolfo, G. Bruce Pike, Ralf Puls, Ivar Reinvang, Miguel E. Rentería, Marcella Rietschel, Joshua L. Roffman, Natalie A. Royle, Dan Rujescu, Jonathan Savitz, Hugo G. Schnack, Knut Schnell, Nina Seiferth, Colin Smith, Vidar M. Steen, Maria C Valdés Hernández, Martijn Van Den Heuvel, Nic J. Van Der Wee, Neeltje E M Van Haren, Joris A. Veltman, Henry Völzke, Robert Walker, Lars T. Westlye, Christopher D. Whelan, Ingrid Agartz, Dorret I. Boomsma, Gianpiero L. Cavalleri, Anders M. Dale, Srdjan Djurovic, Wayne C. Drevets, Peter Hagoort, Jeremy Hall, Andreas Heinz, Clifford R Jr. Jack, Tatiana M. Foroud, Stephanie Le Hellard, Fabio Macciardi, Grant W. Montgomery, Jean Baptiste Poline, David J. Porteous, Sanjay M. Sisodiya, John M. Starr, Jessika Sussmann, Arthur W. Toga, Dick J. Veltman, Henrik Walter, Michael W. Weiner, Joshua C. Bis, M. Arfan Ikram, Albert V. Smith, Vilmundur Gudnason, Christophe Tzourio, Meike W. Vernooij, Lenore J. Launer, Charles Decarli, Sudha Seshadri, Ole A. Andreassen, Liana G. Apostolova, Mark E. Bastin, John Blangero, Han G. Brunner, Randy L. Buckner, Sven Cichon, Giovanni Coppola, Greig I. De Zubicaray, Ian J. Deary, Gary Donohoe, Eco J C De Geus, Thomas Espeseth, Guillén Fernéndez, David C. Glahn, Hans J. Grabe, John Hardy, Hilleke E. Hulshoff Pol, Mark Jenkinson, René S. Kahn, Colm Mcdonald, Andrew M. Mcintosh, Francis J. Mcmahon, Katie L. Mcmahon, Andreas Meyer-Lindenberg, Derek W. Morris, Bertram Müller-Myhsok, Thomas E. Nichols, Roel A. Ophoff, Tomas Paus, Zdenka Pausova, Brenda W. Penninx, Steven G. Potkin, Philipp G. Sämann, Andrew J. Saykin, Gunter Schumann, Jordan W. Smoller, Joanna M. Wardlaw, Michael E. Weale, Nicholas G. Martin, Barbara Franke, Margaret J. Wright, Paul M. Thompson

Research output: Contribution to journalArticle

378 Citations (Scopus)

Abstract

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 × 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 × 10 -12). We also identified a suggestive association with total brain volume at rs10494373 within DDR2 (1q23.3; N = 6,500; P = 5.81 × 10 -7).

Original languageEnglish (US)
Pages (from-to)552-561
Number of pages10
JournalNature Genetics
Volume44
Issue number5
DOIs
StatePublished - May 2012

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Brain
Temporal Lobe Epilepsy
Genome-Wide Association Study
Neuroimaging
Cognition
Meta-Analysis
Hippocampus
Schizophrenia
Alzheimer Disease
Biomarkers
Magnetic Resonance Imaging
Depression
Phenotype
Costs and Cost Analysis
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

Stein, J. L., Medland, S. E., Vasquez, A. A., Hibar, D. P., Senstad, R. E., Winkler, A. M., ... Thompson, P. M. (2012). Identification of common variants associated with human hippocampal and intracranial volumes. Nature Genetics, 44(5), 552-561. https://doi.org/10.1038/ng.2250

Identification of common variants associated with human hippocampal and intracranial volumes. / Stein, Jason L.; Medland, Sarah E.; Vasquez, Alejandro Arias; Hibar, Derrek P.; Senstad, Rudy E.; Winkler, Anderson M.; Toro, Roberto; Appel, Katja; Bartecek, Richard; Bergmann, Ørjan; Bernard, Manon; Brown, Andrew A.; Cannon, Dara M.; Chakravarty, M. Mallar; Christoforou, Andrea; Domin, Martin; Grimm, Oliver; Hollinshead, Marisa; Holmes, Avram J.; Homuth, Georg; Hottenga, Jouke Jan; Langan, Camilla; Lopez, Lorna M.; Hansell, Narelle K.; Hwang, Kristy S.; Kim, Sungeun; Laje, Gonzalo; Lee, Phil H.; Liu, Xinmin; Loth, Eva; Lourdusamy, Anbarasu; Mattingsdal, Morten; Mohnke, Sebastian; Maniega, Susana Muñoz; Nho, Kwangsik; Nugent, Allison C.; O'brien, Carol; Papmeyer, Martina; Pütz, Benno; Ramasamy, Adaikalavan; Rasmussen, Jerod; Rijpkema, Mark; Risacher, Shannon L.; Roddey, J. Cooper; Rose, Emma J.; Ryten, Mina; Shen, Li; Sprooten, Emma; Strengman, Eric; Teumer, Alexander; Trabzuni, Daniah; Turner, Jessica; Van Eijk, Kristel; Van Erp, Theo G M; Van Tol, Marie Jose; Wittfeld, Katharina; Wolf, Christiane; Woudstra, Saskia; Aleman, Andre; Alhusaini, Saud; Almasy, Laura; Binder, Elisabeth B.; Brohawn, David G.; Cantor, Rita M.; Carless, Melanie A.; Corvin, Aiden; Czisch, Michael; Curran, Joanne E.; Davies, Gail; De Almeida, Marcio A A; Delanty, Norman; Depondt, Chantal; Duggirala, Ravi; Dyer, Thomas D.; Erk, Susanne; Fagerness, Jesen; Fox, Peter T.; Freimer, Nelson B.; Gill, Michael; Göring, Harald H H; Hagler, Donald J.; Hoehn, David; Holsboer, Florian; Hoogman, Martine; Hosten, Norbert; Jahanshad, Neda; Johnson, Matthew P.; Kasperaviciute, Dalia; Kent, Jack W.; Kochunov, Peter; Lancaster, Jack L.; Lawrie, Stephen M.; Liewald, David C.; Mandl, René; Matarin, Mar; Mattheisen, Manuel; Meisenzahl, Eva; Melle, Ingrid; Moses, Eric K.; Mühleisen, Thomas W.; Nauck, Matthias; Nöthen, Markus M.; Olvera, Rene L.; Pandolfo, Massimo; Pike, G. Bruce; Puls, Ralf; Reinvang, Ivar; Rentería, Miguel E.; Rietschel, Marcella; Roffman, Joshua L.; Royle, Natalie A.; Rujescu, Dan; Savitz, Jonathan; Schnack, Hugo G.; Schnell, Knut; Seiferth, Nina; Smith, Colin; Steen, Vidar M.; Hernández, Maria C Valdés; Van Den Heuvel, Martijn; Van Der Wee, Nic J.; Van Haren, Neeltje E M; Veltman, Joris A.; Völzke, Henry; Walker, Robert; Westlye, Lars T.; Whelan, Christopher D.; Agartz, Ingrid; Boomsma, Dorret I.; Cavalleri, Gianpiero L.; Dale, Anders M.; Djurovic, Srdjan; Drevets, Wayne C.; Hagoort, Peter; Hall, Jeremy; Heinz, Andreas; Jack, Clifford R Jr.; Foroud, Tatiana M.; Le Hellard, Stephanie; Macciardi, Fabio; Montgomery, Grant W.; Poline, Jean Baptiste; Porteous, David J.; Sisodiya, Sanjay M.; Starr, John M.; Sussmann, Jessika; Toga, Arthur W.; Veltman, Dick J.; Walter, Henrik; Weiner, Michael W.; Bis, Joshua C.; Ikram, M. Arfan; Smith, Albert V.; Gudnason, Vilmundur; Tzourio, Christophe; Vernooij, Meike W.; Launer, Lenore J.; Decarli, Charles; Seshadri, Sudha; Andreassen, Ole A.; Apostolova, Liana G.; Bastin, Mark E.; Blangero, John; Brunner, Han G.; Buckner, Randy L.; Cichon, Sven; Coppola, Giovanni; De Zubicaray, Greig I.; Deary, Ian J.; Donohoe, Gary; De Geus, Eco J C; Espeseth, Thomas; Fernéndez, Guillén; Glahn, David C.; Grabe, Hans J.; Hardy, John; Hulshoff Pol, Hilleke E.; Jenkinson, Mark; Kahn, René S.; Mcdonald, Colm; Mcintosh, Andrew M.; Mcmahon, Francis J.; Mcmahon, Katie L.; Meyer-Lindenberg, Andreas; Morris, Derek W.; Müller-Myhsok, Bertram; Nichols, Thomas E.; Ophoff, Roel A.; Paus, Tomas; Pausova, Zdenka; Penninx, Brenda W.; Potkin, Steven G.; Sämann, Philipp G.; Saykin, Andrew J.; Schumann, Gunter; Smoller, Jordan W.; Wardlaw, Joanna M.; Weale, Michael E.; Martin, Nicholas G.; Franke, Barbara; Wright, Margaret J.; Thompson, Paul M.

In: Nature Genetics, Vol. 44, No. 5, 05.2012, p. 552-561.

Research output: Contribution to journalArticle

Stein, JL, Medland, SE, Vasquez, AA, Hibar, DP, Senstad, RE, Winkler, AM, Toro, R, Appel, K, Bartecek, R, Bergmann, Ø, Bernard, M, Brown, AA, Cannon, DM, Chakravarty, MM, Christoforou, A, Domin, M, Grimm, O, Hollinshead, M, Holmes, AJ, Homuth, G, Hottenga, JJ, Langan, C, Lopez, LM, Hansell, NK, Hwang, KS, Kim, S, Laje, G, Lee, PH, Liu, X, Loth, E, Lourdusamy, A, Mattingsdal, M, Mohnke, S, Maniega, SM, Nho, K, Nugent, AC, O'brien, C, Papmeyer, M, Pütz, B, Ramasamy, A, Rasmussen, J, Rijpkema, M, Risacher, SL, Roddey, JC, Rose, EJ, Ryten, M, Shen, L, Sprooten, E, Strengman, E, Teumer, A, Trabzuni, D, Turner, J, Van Eijk, K, Van Erp, TGM, Van Tol, MJ, Wittfeld, K, Wolf, C, Woudstra, S, Aleman, A, Alhusaini, S, Almasy, L, Binder, EB, Brohawn, DG, Cantor, RM, Carless, MA, Corvin, A, Czisch, M, Curran, JE, Davies, G, De Almeida, MAA, Delanty, N, Depondt, C, Duggirala, R, Dyer, TD, Erk, S, Fagerness, J, Fox, PT, Freimer, NB, Gill, M, Göring, HHH, Hagler, DJ, Hoehn, D, Holsboer, F, Hoogman, M, Hosten, N, Jahanshad, N, Johnson, MP, Kasperaviciute, D, Kent, JW, Kochunov, P, Lancaster, JL, Lawrie, SM, Liewald, DC, Mandl, R, Matarin, M, Mattheisen, M, Meisenzahl, E, Melle, I, Moses, EK, Mühleisen, TW, Nauck, M, Nöthen, MM, Olvera, RL, Pandolfo, M, Pike, GB, Puls, R, Reinvang, I, Rentería, ME, Rietschel, M, Roffman, JL, Royle, NA, Rujescu, D, Savitz, J, Schnack, HG, Schnell, K, Seiferth, N, Smith, C, Steen, VM, Hernández, MCV, Van Den Heuvel, M, Van Der Wee, NJ, Van Haren, NEM, Veltman, JA, Völzke, H, Walker, R, Westlye, LT, Whelan, CD, Agartz, I, Boomsma, DI, Cavalleri, GL, Dale, AM, Djurovic, S, Drevets, WC, Hagoort, P, Hall, J, Heinz, A, Jack, CRJ, Foroud, TM, Le Hellard, S, Macciardi, F, Montgomery, GW, Poline, JB, Porteous, DJ, Sisodiya, SM, Starr, JM, Sussmann, J, Toga, AW, Veltman, DJ, Walter, H, Weiner, MW, Bis, JC, Ikram, MA, Smith, AV, Gudnason, V, Tzourio, C, Vernooij, MW, Launer, LJ, Decarli, C, Seshadri, S, Andreassen, OA, Apostolova, LG, Bastin, ME, Blangero, J, Brunner, HG, Buckner, RL, Cichon, S, Coppola, G, De Zubicaray, GI, Deary, IJ, Donohoe, G, De Geus, EJC, Espeseth, T, Fernéndez, G, Glahn, DC, Grabe, HJ, Hardy, J, Hulshoff Pol, HE, Jenkinson, M, Kahn, RS, Mcdonald, C, Mcintosh, AM, Mcmahon, FJ, Mcmahon, KL, Meyer-Lindenberg, A, Morris, DW, Müller-Myhsok, B, Nichols, TE, Ophoff, RA, Paus, T, Pausova, Z, Penninx, BW, Potkin, SG, Sämann, PG, Saykin, AJ, Schumann, G, Smoller, JW, Wardlaw, JM, Weale, ME, Martin, NG, Franke, B, Wright, MJ & Thompson, PM 2012, 'Identification of common variants associated with human hippocampal and intracranial volumes', Nature Genetics, vol. 44, no. 5, pp. 552-561. https://doi.org/10.1038/ng.2250
Stein JL, Medland SE, Vasquez AA, Hibar DP, Senstad RE, Winkler AM et al. Identification of common variants associated with human hippocampal and intracranial volumes. Nature Genetics. 2012 May;44(5):552-561. https://doi.org/10.1038/ng.2250
Stein, Jason L. ; Medland, Sarah E. ; Vasquez, Alejandro Arias ; Hibar, Derrek P. ; Senstad, Rudy E. ; Winkler, Anderson M. ; Toro, Roberto ; Appel, Katja ; Bartecek, Richard ; Bergmann, Ørjan ; Bernard, Manon ; Brown, Andrew A. ; Cannon, Dara M. ; Chakravarty, M. Mallar ; Christoforou, Andrea ; Domin, Martin ; Grimm, Oliver ; Hollinshead, Marisa ; Holmes, Avram J. ; Homuth, Georg ; Hottenga, Jouke Jan ; Langan, Camilla ; Lopez, Lorna M. ; Hansell, Narelle K. ; Hwang, Kristy S. ; Kim, Sungeun ; Laje, Gonzalo ; Lee, Phil H. ; Liu, Xinmin ; Loth, Eva ; Lourdusamy, Anbarasu ; Mattingsdal, Morten ; Mohnke, Sebastian ; Maniega, Susana Muñoz ; Nho, Kwangsik ; Nugent, Allison C. ; O'brien, Carol ; Papmeyer, Martina ; Pütz, Benno ; Ramasamy, Adaikalavan ; Rasmussen, Jerod ; Rijpkema, Mark ; Risacher, Shannon L. ; Roddey, J. Cooper ; Rose, Emma J. ; Ryten, Mina ; Shen, Li ; Sprooten, Emma ; Strengman, Eric ; Teumer, Alexander ; Trabzuni, Daniah ; Turner, Jessica ; Van Eijk, Kristel ; Van Erp, Theo G M ; Van Tol, Marie Jose ; Wittfeld, Katharina ; Wolf, Christiane ; Woudstra, Saskia ; Aleman, Andre ; Alhusaini, Saud ; Almasy, Laura ; Binder, Elisabeth B. ; Brohawn, David G. ; Cantor, Rita M. ; Carless, Melanie A. ; Corvin, Aiden ; Czisch, Michael ; Curran, Joanne E. ; Davies, Gail ; De Almeida, Marcio A A ; Delanty, Norman ; Depondt, Chantal ; Duggirala, Ravi ; Dyer, Thomas D. ; Erk, Susanne ; Fagerness, Jesen ; Fox, Peter T. ; Freimer, Nelson B. ; Gill, Michael ; Göring, Harald H H ; Hagler, Donald J. ; Hoehn, David ; Holsboer, Florian ; Hoogman, Martine ; Hosten, Norbert ; Jahanshad, Neda ; Johnson, Matthew P. ; Kasperaviciute, Dalia ; Kent, Jack W. ; Kochunov, Peter ; Lancaster, Jack L. ; Lawrie, Stephen M. ; Liewald, David C. ; Mandl, René ; Matarin, Mar ; Mattheisen, Manuel ; Meisenzahl, Eva ; Melle, Ingrid ; Moses, Eric K. ; Mühleisen, Thomas W. ; Nauck, Matthias ; Nöthen, Markus M. ; Olvera, Rene L. ; Pandolfo, Massimo ; Pike, G. Bruce ; Puls, Ralf ; Reinvang, Ivar ; Rentería, Miguel E. ; Rietschel, Marcella ; Roffman, Joshua L. ; Royle, Natalie A. ; Rujescu, Dan ; Savitz, Jonathan ; Schnack, Hugo G. ; Schnell, Knut ; Seiferth, Nina ; Smith, Colin ; Steen, Vidar M. ; Hernández, Maria C Valdés ; Van Den Heuvel, Martijn ; Van Der Wee, Nic J. ; Van Haren, Neeltje E M ; Veltman, Joris A. ; Völzke, Henry ; Walker, Robert ; Westlye, Lars T. ; Whelan, Christopher D. ; Agartz, Ingrid ; Boomsma, Dorret I. ; Cavalleri, Gianpiero L. ; Dale, Anders M. ; Djurovic, Srdjan ; Drevets, Wayne C. ; Hagoort, Peter ; Hall, Jeremy ; Heinz, Andreas ; Jack, Clifford R Jr. ; Foroud, Tatiana M. ; Le Hellard, Stephanie ; Macciardi, Fabio ; Montgomery, Grant W. ; Poline, Jean Baptiste ; Porteous, David J. ; Sisodiya, Sanjay M. ; Starr, John M. ; Sussmann, Jessika ; Toga, Arthur W. ; Veltman, Dick J. ; Walter, Henrik ; Weiner, Michael W. ; Bis, Joshua C. ; Ikram, M. Arfan ; Smith, Albert V. ; Gudnason, Vilmundur ; Tzourio, Christophe ; Vernooij, Meike W. ; Launer, Lenore J. ; Decarli, Charles ; Seshadri, Sudha ; Andreassen, Ole A. ; Apostolova, Liana G. ; Bastin, Mark E. ; Blangero, John ; Brunner, Han G. ; Buckner, Randy L. ; Cichon, Sven ; Coppola, Giovanni ; De Zubicaray, Greig I. ; Deary, Ian J. ; Donohoe, Gary ; De Geus, Eco J C ; Espeseth, Thomas ; Fernéndez, Guillén ; Glahn, David C. ; Grabe, Hans J. ; Hardy, John ; Hulshoff Pol, Hilleke E. ; Jenkinson, Mark ; Kahn, René S. ; Mcdonald, Colm ; Mcintosh, Andrew M. ; Mcmahon, Francis J. ; Mcmahon, Katie L. ; Meyer-Lindenberg, Andreas ; Morris, Derek W. ; Müller-Myhsok, Bertram ; Nichols, Thomas E. ; Ophoff, Roel A. ; Paus, Tomas ; Pausova, Zdenka ; Penninx, Brenda W. ; Potkin, Steven G. ; Sämann, Philipp G. ; Saykin, Andrew J. ; Schumann, Gunter ; Smoller, Jordan W. ; Wardlaw, Joanna M. ; Weale, Michael E. ; Martin, Nicholas G. ; Franke, Barbara ; Wright, Margaret J. ; Thompson, Paul M. / Identification of common variants associated with human hippocampal and intracranial volumes. In: Nature Genetics. 2012 ; Vol. 44, No. 5. pp. 552-561.
@article{517388bd55d74491a2312f87193c7ce8,
title = "Identification of common variants associated with human hippocampal and intracranial volumes",
abstract = "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 × 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 × 10 -12). We also identified a suggestive association with total brain volume at rs10494373 within DDR2 (1q23.3; N = 6,500; P = 5.81 × 10 -7).",
author = "Stein, {Jason L.} and Medland, {Sarah E.} and Vasquez, {Alejandro Arias} and Hibar, {Derrek P.} and Senstad, {Rudy E.} and Winkler, {Anderson M.} and Roberto Toro and Katja Appel and Richard Bartecek and {\O}rjan Bergmann and Manon Bernard and Brown, {Andrew A.} and Cannon, {Dara M.} and Chakravarty, {M. Mallar} and Andrea Christoforou and Martin Domin and Oliver Grimm and Marisa Hollinshead and Holmes, {Avram J.} and Georg Homuth and Hottenga, {Jouke Jan} and Camilla Langan and Lopez, {Lorna M.} and Hansell, {Narelle K.} and Hwang, {Kristy S.} and Sungeun Kim and Gonzalo Laje and Lee, {Phil H.} and Xinmin Liu and Eva Loth and Anbarasu Lourdusamy and Morten Mattingsdal and Sebastian Mohnke and Maniega, {Susana Mu{\~n}oz} and Kwangsik Nho and Nugent, {Allison C.} and Carol O'brien and Martina Papmeyer and Benno P{\"u}tz and Adaikalavan Ramasamy and Jerod Rasmussen and Mark Rijpkema and Risacher, {Shannon L.} and Roddey, {J. Cooper} and Rose, {Emma J.} and Mina Ryten and Li Shen and Emma Sprooten and Eric Strengman and Alexander Teumer and Daniah Trabzuni and Jessica Turner and {Van Eijk}, Kristel and {Van Erp}, {Theo G M} and {Van Tol}, {Marie Jose} and Katharina Wittfeld and Christiane Wolf and Saskia Woudstra and Andre Aleman and Saud Alhusaini and Laura Almasy and Binder, {Elisabeth B.} and Brohawn, {David G.} and Cantor, {Rita M.} and Carless, {Melanie A.} and Aiden Corvin and Michael Czisch and Curran, {Joanne E.} and Gail Davies and {De Almeida}, {Marcio A A} and Norman Delanty and Chantal Depondt and Ravi Duggirala and Dyer, {Thomas D.} and Susanne Erk and Jesen Fagerness and Fox, {Peter T.} and Freimer, {Nelson B.} and Michael Gill and G{\"o}ring, {Harald H H} and Hagler, {Donald J.} and David Hoehn and Florian Holsboer and Martine Hoogman and Norbert Hosten and Neda Jahanshad and Johnson, {Matthew P.} and Dalia Kasperaviciute and Kent, {Jack W.} and Peter Kochunov and Lancaster, {Jack L.} and Lawrie, {Stephen M.} and Liewald, {David C.} and Ren{\'e} Mandl and Mar Matarin and Manuel Mattheisen and Eva Meisenzahl and Ingrid Melle and Moses, {Eric K.} and M{\"u}hleisen, {Thomas W.} and Matthias Nauck and N{\"o}then, {Markus M.} and Olvera, {Rene L.} and Massimo Pandolfo and Pike, {G. Bruce} and Ralf Puls and Ivar Reinvang and Renter{\'i}a, {Miguel E.} and Marcella Rietschel and Roffman, {Joshua L.} and Royle, {Natalie A.} and Dan Rujescu and Jonathan Savitz and Schnack, {Hugo G.} and Knut Schnell and Nina Seiferth and Colin Smith and Steen, {Vidar M.} and Hern{\'a}ndez, {Maria C Vald{\'e}s} and {Van Den Heuvel}, Martijn and {Van Der Wee}, {Nic J.} and {Van Haren}, {Neeltje E M} and Veltman, {Joris A.} and Henry V{\"o}lzke and Robert Walker and Westlye, {Lars T.} and Whelan, {Christopher D.} and Ingrid Agartz and Boomsma, {Dorret I.} and Cavalleri, {Gianpiero L.} and Dale, {Anders M.} and Srdjan Djurovic and Drevets, {Wayne C.} and Peter Hagoort and Jeremy Hall and Andreas Heinz and Jack, {Clifford R Jr.} and Foroud, {Tatiana M.} and {Le Hellard}, Stephanie and Fabio Macciardi and Montgomery, {Grant W.} and Poline, {Jean Baptiste} and Porteous, {David J.} and Sisodiya, {Sanjay M.} and Starr, {John M.} and Jessika Sussmann and Toga, {Arthur W.} and Veltman, {Dick J.} and Henrik Walter and Weiner, {Michael W.} and Bis, {Joshua C.} and Ikram, {M. Arfan} and Smith, {Albert V.} and Vilmundur Gudnason and Christophe Tzourio and Vernooij, {Meike W.} and Launer, {Lenore J.} and Charles Decarli and Sudha Seshadri and Andreassen, {Ole A.} and Apostolova, {Liana G.} and Bastin, {Mark E.} and John Blangero and Brunner, {Han G.} and Buckner, {Randy L.} and Sven Cichon and Giovanni Coppola and {De Zubicaray}, {Greig I.} and Deary, {Ian J.} and Gary Donohoe and {De Geus}, {Eco J C} and Thomas Espeseth and Guill{\'e}n Fern{\'e}ndez and Glahn, {David C.} and Grabe, {Hans J.} and John Hardy and {Hulshoff Pol}, {Hilleke E.} and Mark Jenkinson and Kahn, {Ren{\'e} S.} and Colm Mcdonald and Mcintosh, {Andrew M.} and Mcmahon, {Francis J.} and Mcmahon, {Katie L.} and Andreas Meyer-Lindenberg and Morris, {Derek W.} and Bertram M{\"u}ller-Myhsok and Nichols, {Thomas E.} and Ophoff, {Roel A.} and Tomas Paus and Zdenka Pausova and Penninx, {Brenda W.} and Potkin, {Steven G.} and S{\"a}mann, {Philipp G.} and Saykin, {Andrew J.} and Gunter Schumann and Smoller, {Jordan W.} and Wardlaw, {Joanna M.} and Weale, {Michael E.} and Martin, {Nicholas G.} and Barbara Franke and Wright, {Margaret J.} and Thompson, {Paul M.}",
year = "2012",
month = "5",
doi = "10.1038/ng.2250",
language = "English (US)",
volume = "44",
pages = "552--561",
journal = "Nature Genetics",
issn = "1061-4036",
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TY - JOUR

T1 - Identification of common variants associated with human hippocampal and intracranial volumes

AU - Stein, Jason L.

AU - Medland, Sarah E.

AU - Vasquez, Alejandro Arias

AU - Hibar, Derrek P.

AU - Senstad, Rudy E.

AU - Winkler, Anderson M.

AU - Toro, Roberto

AU - Appel, Katja

AU - Bartecek, Richard

AU - Bergmann, Ørjan

AU - Bernard, Manon

AU - Brown, Andrew A.

AU - Cannon, Dara M.

AU - Chakravarty, M. Mallar

AU - Christoforou, Andrea

AU - Domin, Martin

AU - Grimm, Oliver

AU - Hollinshead, Marisa

AU - Holmes, Avram J.

AU - Homuth, Georg

AU - Hottenga, Jouke Jan

AU - Langan, Camilla

AU - Lopez, Lorna M.

AU - Hansell, Narelle K.

AU - Hwang, Kristy S.

AU - Kim, Sungeun

AU - Laje, Gonzalo

AU - Lee, Phil H.

AU - Liu, Xinmin

AU - Loth, Eva

AU - Lourdusamy, Anbarasu

AU - Mattingsdal, Morten

AU - Mohnke, Sebastian

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PY - 2012/5

Y1 - 2012/5

N2 - 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 × 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 × 10 -12). We also identified a suggestive association with total brain volume at rs10494373 within DDR2 (1q23.3; N = 6,500; P = 5.81 × 10 -7).

AB - 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 × 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 × 10 -12). We also identified a suggestive association with total brain volume at rs10494373 within DDR2 (1q23.3; N = 6,500; P = 5.81 × 10 -7).

UR - http://www.scopus.com/inward/record.url?scp=84860351742&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84860351742&partnerID=8YFLogxK

U2 - 10.1038/ng.2250

DO - 10.1038/ng.2250

M3 - Article

VL - 44

SP - 552

EP - 561

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 5

ER -