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 language | English (US) |
|---|---|
| Pages (from-to) | 552-561 |
| Number of pages | 10 |
| Journal | Nature Genetics |
| Volume | 44 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 2012 |
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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.; 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 journal › Article
}
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
AU - Maniega, Susana Muñoz
AU - Nho, Kwangsik
AU - Nugent, Allison C.
AU - O'brien, Carol
AU - Papmeyer, Martina
AU - Pütz, Benno
AU - Ramasamy, Adaikalavan
AU - Rasmussen, Jerod
AU - Rijpkema, Mark
AU - Risacher, Shannon L.
AU - Roddey, J. Cooper
AU - Rose, Emma J.
AU - Ryten, Mina
AU - Shen, Li
AU - Sprooten, Emma
AU - Strengman, Eric
AU - Teumer, Alexander
AU - Trabzuni, Daniah
AU - Turner, Jessica
AU - Van Eijk, Kristel
AU - Van Erp, Theo G M
AU - Van Tol, Marie Jose
AU - Wittfeld, Katharina
AU - Wolf, Christiane
AU - Woudstra, Saskia
AU - Aleman, Andre
AU - Alhusaini, Saud
AU - Almasy, Laura
AU - Binder, Elisabeth B.
AU - Brohawn, David G.
AU - Cantor, Rita M.
AU - Carless, Melanie A.
AU - Corvin, Aiden
AU - Czisch, Michael
AU - Curran, Joanne E.
AU - Davies, Gail
AU - De Almeida, Marcio A A
AU - Delanty, Norman
AU - Depondt, Chantal
AU - Duggirala, Ravi
AU - Dyer, Thomas D.
AU - Erk, Susanne
AU - Fagerness, Jesen
AU - Fox, Peter T.
AU - Freimer, Nelson B.
AU - Gill, Michael
AU - Göring, Harald H H
AU - Hagler, Donald J.
AU - Hoehn, David
AU - Holsboer, Florian
AU - Hoogman, Martine
AU - Hosten, Norbert
AU - Jahanshad, Neda
AU - Johnson, Matthew P.
AU - Kasperaviciute, Dalia
AU - Kent, Jack W.
AU - Kochunov, Peter
AU - Lancaster, Jack L.
AU - Lawrie, Stephen M.
AU - Liewald, David C.
AU - Mandl, René
AU - Matarin, Mar
AU - Mattheisen, Manuel
AU - Meisenzahl, Eva
AU - Melle, Ingrid
AU - Moses, Eric K.
AU - Mühleisen, Thomas W.
AU - Nauck, Matthias
AU - Nöthen, Markus M.
AU - Olvera, Rene L.
AU - Pandolfo, Massimo
AU - Pike, G. Bruce
AU - Puls, Ralf
AU - Reinvang, Ivar
AU - Rentería, Miguel E.
AU - Rietschel, Marcella
AU - Roffman, Joshua L.
AU - Royle, Natalie A.
AU - Rujescu, Dan
AU - Savitz, Jonathan
AU - Schnack, Hugo G.
AU - Schnell, Knut
AU - Seiferth, Nina
AU - Smith, Colin
AU - Steen, Vidar M.
AU - Hernández, Maria C Valdés
AU - Van Den Heuvel, Martijn
AU - Van Der Wee, Nic J.
AU - Van Haren, Neeltje E M
AU - Veltman, Joris A.
AU - Völzke, Henry
AU - Walker, Robert
AU - Westlye, Lars T.
AU - Whelan, Christopher D.
AU - Agartz, Ingrid
AU - Boomsma, Dorret I.
AU - Cavalleri, Gianpiero L.
AU - Dale, Anders M.
AU - Djurovic, Srdjan
AU - Drevets, Wayne C.
AU - Hagoort, Peter
AU - Hall, Jeremy
AU - Heinz, Andreas
AU - Jack, Clifford R.
AU - Foroud, Tatiana M.
AU - Le Hellard, Stephanie
AU - Macciardi, Fabio
AU - Montgomery, Grant W.
AU - Poline, Jean Baptiste
AU - Porteous, David J.
AU - Sisodiya, Sanjay M.
AU - Starr, John M.
AU - Sussmann, Jessika
AU - Toga, Arthur W.
AU - Veltman, Dick J.
AU - Walter, Henrik
AU - Weiner, Michael W.
AU - Bis, Joshua C.
AU - Ikram, M. Arfan
AU - Smith, Albert V.
AU - Gudnason, Vilmundur
AU - Tzourio, Christophe
AU - Vernooij, Meike W.
AU - Launer, Lenore J.
AU - DeCarli, Charles
AU - Seshadri, Sudha
AU - Andreassen, Ole A.
AU - Apostolova, Liana G.
AU - Bastin, Mark E.
AU - Blangero, John
AU - Brunner, Han G.
AU - Buckner, Randy L.
AU - Cichon, Sven
AU - Coppola, Giovanni
AU - De Zubicaray, Greig I.
AU - Deary, Ian J.
AU - Donohoe, Gary
AU - De Geus, Eco J C
AU - Espeseth, Thomas
AU - Fernéndez, Guillén
AU - Glahn, David C.
AU - Grabe, Hans J.
AU - Hardy, John
AU - Hulshoff Pol, Hilleke E.
AU - Jenkinson, Mark
AU - Kahn, René S.
AU - Mcdonald, Colm
AU - Mcintosh, Andrew M.
AU - Mcmahon, Francis J.
AU - Mcmahon, Katie L.
AU - Meyer-Lindenberg, Andreas
AU - Morris, Derek W.
AU - Müller-Myhsok, Bertram
AU - Nichols, Thomas E.
AU - Ophoff, Roel A.
AU - Paus, Tomas
AU - Pausova, Zdenka
AU - Penninx, Brenda W.
AU - Potkin, Steven G.
AU - Sämann, Philipp G.
AU - Saykin, Andrew J.
AU - Schumann, Gunter
AU - Smoller, Jordan W.
AU - Wardlaw, Joanna M.
AU - Weale, Michael E.
AU - Martin, Nicholas G.
AU - Franke, Barbara
AU - Wright, Margaret J.
AU - Thompson, Paul M.
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
C2 - 22504417
AN - SCOPUS:84860351742
VL - 44
SP - 552
EP - 561
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 5
ER -