Novel genetic loci associated with hippocampal volume

Hibar, Derrek P., Adams, Hieab H. H., Jahanshad, Neda, Chauhan, Ganesh, Stein, Jason L., Hofer, Edith, Renteria, Miguel E., Bis, Joshua C., Arias-Vasquez, Alejandro, Ikram, M. Kamran, Desrivieres, Sylvane, Vernooij, Meike W., Abramovic, Lucija, Alhusaini, Saud, Amin, Najaf, Andersson, Micael, Arfanakis, Konstantinos, Aribisala, Benjamin S., Armstrong, Nicola J., Athanasiu, Lavinia, Axelsson, Tomas, Beecham, Ashley H., Beiser, Alexa, Bernard, Manon, Blanton, Susan H., Bohlken, Marc M., Boks, Marco P., Bralten, Janita, Brickman, Adam M., Carmichael, Owen, Chakravarty, M. Mallar, Chen, Qiang, Ching, Christopher R. K., Chouraki, Vincent, Cuellar-Partida, Gabriel, Crivello, Fabrice, Den Braber, Anouk, Doan, Nhat Trung, Ehrlich, Stefan, Giddaluru, Sudheer, Goldman, Aaron L., Gottesman, Rebecca F., Grimm, Oliver, Griswold, Michael E., Guadalupe, Tulio, Gutman, Boris A., Hass, Johanna, Haukvik, Unn K., Hoehn, David, Holmes, Avram J., Hoogman, Martine, Janowitz, Deborah, Jia, Tianye, Jorgensen, Kjetil N., Karbalai, Nazanin, Kasperaviciute, Dalia, Kim, Sungeun, Klein, Marieke, Kraemer, Bernd, Lee, Phil H., Liewald, David C. M., Lopez, Lorna M., Luciano, Michelle, Macare, Christine, Marquand, Andre F, Matarin, Mar, Mather, Karen A., Mattheisen, Manuel, McKay, David R., Milaneschi, Yuri, Munoz Maniega, Susana, Nho, Kwangsik, Nugent, Allison C., Nyquist, Paul, Loohuis, Loes M. Olde, Oosterlaan, Jaap, Papmeyer, Martina, Pirpamer, Lukas, Putz, Benno, Ramasamy, Adaikalavan, Richards, Jennifer S., Risacher, Shannon L., Roiz-Santianez, Roberto, Rommelse, Nanda, Ropele, Stefan, Rose, Emma J., Royle, Natalie A., Rundek, Tatjana, Samann, Philipp G., Saremi, Arvin, Satizabal, Claudia L, Schmaal, Lianne, Schork, Andrew J., Shen, Li, Shin, Jean, Shumskaya, Elena, Smith, Albert V., Sprooten, Emma, Strike, Lachlan T., Teumer, Alexander, Tordesillas-Gutierrez, Diana, Toro, Roberto, Trabzuni, Daniah, Trompet, Stella, Vaidya, Dhananjay, Van Der Grond, Jeroen, Van Der Lee, Sven J., Van Der Meer, Dennis, Van Donkelaar, Marjolein M. J., Van Eijk, Kristel R., Van Erp, Theo G. M., Van Rooij, Daan, Walton, Esther, Westlye, Lars T., Whelan, Christopher D., Windham, Beverly G., Winkler, Anderson M., Wittfeld, Katharina, Woldehawariat, Girma, Wolf, Christiane, Wolfers, Thomas, Yanek, Lisa R., Yang, Jingyun, Zijdenbos, Alex, Zwiers, Marcel P., Agartz, Ingrid, Almasy, Laura, Ames, David, Amouyel, Philippe, Andreassen, Ole A., Arepalli, Sampath, Assareh, Amelia A., Barral, Sandra, Bastin, Mark E., Becker, Diane M., Becker, James T., Bennett, David A., Blangero, John, Van Bokhoven, Hans, Boomsma, Dorret I., Brodaty, Henry, Brouwer, Rachel M., Brunner, Han G., Buckner, Randy L., Buitelaar, Jan K., Bulayeva, Kazima B., Cahn, Wiepke, Calhoun, Vince D., Cannon, Dara M., Cavalleri, Gianpiero L., Cheng, Ching-Yu, Cichon, Sven, Cookson, Mark R., Corvin, Aiden, Crespo-Facorro, Benedicto, Curran, Joanne E., Czisch, Michael, Dale, Anders M., Davies, Gareth E., De Craen, Anton J. M., De Geus, Eco J. C., De Jager, Philip L., De Zubicaray, Greig I., Deary, Ian J., Debette, Stephanie, Decarli, Charles, Delanty, Norman, Depondt, Chantal, Destefano, Anita, Dillman, Allissa, Djurovic, Srdjan, Donohoe, Gary, Drevets, Wayne C., Duggirala, Ravi, Dyer, Thomas D., Enzinger, Christian, Erk, Susanne, Espeseth, Thomas, Fedko, Iryna O., Fernandez, Guillen, Ferrucci, Luigi, Fisher, Simon E., Fleischman, Debra A., Ford, Ian, Fornage, Myriam, Foroud, Tatiana M., Fox, Peter T., Francks, Clyde, Fukunaga, Masaki, Gibbs, J. Raphael, Glahn, David C., Gollub, Randy L., Goring, Harald H. H., Green, Robert C., Gruber, Oliver, Gudnason, Vilmundur, Guelfi, Sebastian, Haberg, Asta K., Hansell, Narelle K., Hardy, John, Hartman, Catharina A., Hashimoto, Ryota, Hegenscheid, Katrin, Heinz, Andreas, Le Hellard, Stephanie, Hernandez, Dena G., Heslenfeld, Dirk J., Ho, Beng-Choon, Hoekstra, Pieter J., Hoffmann, Wolfgang, Hofman, Albert, Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Hottenga, Jouke-Jan, Huentelman, Matthew, Pol, Hilleke E. Hulshoff, Ikeda, Masashi, Jack, Clifford R., Jenkinson, Mark, Johnson, Robert, Joensson, Erik G., Jukema, J. Wouter, Kahn, Rene S., Kanai, Ryota, Kloszewska, Iwona, Knopman, David S., Kochunov, Peter, Kwok, John B., Lawrie, Stephen M., Lemaitre, Herve, Liu, Xinmin, Longo, Dan L., Lopez, Oscar L., Lovestone, Simon, Martinez, Oliver, Martinot, Jean-Luc, Mattay, Venkata S., McDonald, Colm, McIntosh, Andrew M., McMahon, Francis J., McMahon, Katie L., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Mohnke, Sebastian, Montgomery, Grant W., Morris, Derek W., Mosley, Thomas H., Muhleisen, Thomas W., Muller-Myhsok, Bertram, Nalls, Michael A., Nauck, Matthias, Nichols, Thomas E., Niessen, Wiro J., Nothen, Markus M., Nyberg, Lars, Ohi, Kazutaka, Olvera, Rene L., Ophoff, Roel A., Pandolfo, Massimo, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W. J. H., Pike, G. Bruce, Potkin, Steven G., Psaty, Bruce M., Reppermund, Simone, Rietschel, Marcella, Roffman, Joshua L., Romanczuk-Seiferth, Nina, Rotter, Jerome I., Ryten, Mina, Sacco, Ralph L., Sachdev, Perminder S., Saykin, Andrew J., Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter R., Sigursson, Sigurdur, Simmons, Andrew, Singleton, Andrew, Sisodiya, Sanjay M., Smith, Colin, Smoller, Jordan W., Soininen, Hilkka, Steen, Vidar M., Stott, David J., Sussmann, Jessika E., Thalamuthu, Anbupalam, Toga, Arthur W., Traynor, Bryan J., Troncoso, Juan, Tsolaki, Magda, Tzourio, Christophe, Uitterlinden, Andre G., Hernandez, Maria C. Valdes, Van Der Brug, Marcel, Van Der Lugt, Aad, Van Der Wee, Nic J. A., Van Haren, Neeltje E. M., Van 'T Ent, Dennis, Van Tol, Marie-Jose, Vardarajan, Badri N., Vellas, Bruno, Veltman, Dick J., Volzke, Henry, Walter, Henrik, Wardlaw, Joanna M., Wassink, Thomas H., Weale, Michael E., Weinberger, Daniel R., Weiner, Michael W., Wen, Wei, Westman, Eric, White, Tonya, Wong, Tien Y., Wright, Clinton B., Zielke, Ronald H., Zonderman, Alan B., Martin, Nicholas G., Van Duijn, Cornelia M., Wright, Margaret J., Longstreth, W. T., Schumann, Gunter, Grabe, Hans J., Franke, Barbara, Launer, Lenore J., Medland, Sarah E., Seshadri, Sudha, Thompson, Paul M. and Ikram, M. Arfan (2017) Novel genetic loci associated with hippocampal volume. Nature Communications, 8 13624-13624. doi:10.1038/ncomms13624


Author Hibar, Derrek P.
Adams, Hieab H. H.
Jahanshad, Neda
Chauhan, Ganesh
Stein, Jason L.
Hofer, Edith
Renteria, Miguel E.
Bis, Joshua C.
Arias-Vasquez, Alejandro
Ikram, M. Kamran
Desrivieres, Sylvane
Vernooij, Meike W.
Abramovic, Lucija
Alhusaini, Saud
Amin, Najaf
Andersson, Micael
Arfanakis, Konstantinos
Aribisala, Benjamin S.
Armstrong, Nicola J.
Athanasiu, Lavinia
Axelsson, Tomas
Beecham, Ashley H.
Beiser, Alexa
Bernard, Manon
Blanton, Susan H.
Bohlken, Marc M.
Boks, Marco P.
Bralten, Janita
Brickman, Adam M.
Carmichael, Owen
Chakravarty, M. Mallar
Chen, Qiang
Ching, Christopher R. K.
Chouraki, Vincent
Cuellar-Partida, Gabriel
Crivello, Fabrice
Den Braber, Anouk
Doan, Nhat Trung
Ehrlich, Stefan
Giddaluru, Sudheer
Goldman, Aaron L.
Gottesman, Rebecca F.
Grimm, Oliver
Griswold, Michael E.
Guadalupe, Tulio
Gutman, Boris A.
Hass, Johanna
Haukvik, Unn K.
Hoehn, David
Holmes, Avram J.
Hoogman, Martine
Janowitz, Deborah
Jia, Tianye
Jorgensen, Kjetil N.
Karbalai, Nazanin
Kasperaviciute, Dalia
Kim, Sungeun
Klein, Marieke
Kraemer, Bernd
Lee, Phil H.
Liewald, David C. M.
Lopez, Lorna M.
Luciano, Michelle
Macare, Christine
Marquand, Andre F
Matarin, Mar
Mather, Karen A.
Mattheisen, Manuel
McKay, David R.
Milaneschi, Yuri
Munoz Maniega, Susana
Nho, Kwangsik
Nugent, Allison C.
Nyquist, Paul
Loohuis, Loes M. Olde
Oosterlaan, Jaap
Papmeyer, Martina
Pirpamer, Lukas
Putz, Benno
Ramasamy, Adaikalavan
Richards, Jennifer S.
Risacher, Shannon L.
Roiz-Santianez, Roberto
Rommelse, Nanda
Ropele, Stefan
Rose, Emma J.
Royle, Natalie A.
Rundek, Tatjana
Samann, Philipp G.
Saremi, Arvin
Satizabal, Claudia L
Schmaal, Lianne
Schork, Andrew J.
Shen, Li
Shin, Jean
Shumskaya, Elena
Smith, Albert V.
Sprooten, Emma
Strike, Lachlan T.
Teumer, Alexander
Tordesillas-Gutierrez, Diana
Toro, Roberto
Trabzuni, Daniah
Trompet, Stella
Vaidya, Dhananjay
Van Der Grond, Jeroen
Van Der Lee, Sven J.
Van Der Meer, Dennis
Van Donkelaar, Marjolein M. J.
Van Eijk, Kristel R.
Van Erp, Theo G. M.
Van Rooij, Daan
Walton, Esther
Westlye, Lars T.
Whelan, Christopher D.
Windham, Beverly G.
Winkler, Anderson M.
Wittfeld, Katharina
Woldehawariat, Girma
Wolf, Christiane
Wolfers, Thomas
Yanek, Lisa R.
Yang, Jingyun
Zijdenbos, Alex
Zwiers, Marcel P.
Agartz, Ingrid
Almasy, Laura
Ames, David
Amouyel, Philippe
Andreassen, Ole A.
Arepalli, Sampath
Assareh, Amelia A.
Barral, Sandra
Bastin, Mark E.
Becker, Diane M.
Becker, James T.
Bennett, David A.
Blangero, John
Van Bokhoven, Hans
Boomsma, Dorret I.
Brodaty, Henry
Brouwer, Rachel M.
Brunner, Han G.
Buckner, Randy L.
Buitelaar, Jan K.
Bulayeva, Kazima B.
Cahn, Wiepke
Calhoun, Vince D.
Cannon, Dara M.
Cavalleri, Gianpiero L.
Cheng, Ching-Yu
Cichon, Sven
Cookson, Mark R.
Corvin, Aiden
Crespo-Facorro, Benedicto
Curran, Joanne E.
Czisch, Michael
Dale, Anders M.
Davies, Gareth E.
De Craen, Anton J. M.
De Geus, Eco J. C.
De Jager, Philip L.
De Zubicaray, Greig I.
Deary, Ian J.
Debette, Stephanie
Decarli, Charles
Delanty, Norman
Depondt, Chantal
Destefano, Anita
Dillman, Allissa
Djurovic, Srdjan
Donohoe, Gary
Drevets, Wayne C.
Duggirala, Ravi
Dyer, Thomas D.
Enzinger, Christian
Erk, Susanne
Espeseth, Thomas
Fedko, Iryna O.
Fernandez, Guillen
Ferrucci, Luigi
Fisher, Simon E.
Fleischman, Debra A.
Ford, Ian
Fornage, Myriam
Foroud, Tatiana M.
Fox, Peter T.
Francks, Clyde
Fukunaga, Masaki
Gibbs, J. Raphael
Glahn, David C.
Gollub, Randy L.
Goring, Harald H. H.
Green, Robert C.
Gruber, Oliver
Gudnason, Vilmundur
Guelfi, Sebastian
Haberg, Asta K.
Hansell, Narelle K.
Hardy, John
Hartman, Catharina A.
Hashimoto, Ryota
Hegenscheid, Katrin
Heinz, Andreas
Le Hellard, Stephanie
Hernandez, Dena G.
Heslenfeld, Dirk J.
Ho, Beng-Choon
Hoekstra, Pieter J.
Hoffmann, Wolfgang
Hofman, Albert
Holsboer, Florian
Homuth, Georg
Hosten, Norbert
Hottenga, Jouke-Jan
Huentelman, Matthew
Pol, Hilleke E. Hulshoff
Ikeda, Masashi
Jack, Clifford R.
Jenkinson, Mark
Johnson, Robert
Joensson, Erik G.
Jukema, J. Wouter
Kahn, Rene S.
Kanai, Ryota
Kloszewska, Iwona
Knopman, David S.
Kochunov, Peter
Kwok, John B.
Lawrie, Stephen M.
Lemaitre, Herve
Liu, Xinmin
Longo, Dan L.
Lopez, Oscar L.
Lovestone, Simon
Martinez, Oliver
Martinot, Jean-Luc
Mattay, Venkata S.
McDonald, Colm
McIntosh, Andrew M.
McMahon, Francis J.
McMahon, Katie L.
Mecocci, Patrizia
Melle, Ingrid
Meyer-Lindenberg, Andreas
Mohnke, Sebastian
Montgomery, Grant W.
Morris, Derek W.
Mosley, Thomas H.
Muhleisen, Thomas W.
Muller-Myhsok, Bertram
Nalls, Michael A.
Nauck, Matthias
Nichols, Thomas E.
Niessen, Wiro J.
Nothen, Markus M.
Nyberg, Lars
Ohi, Kazutaka
Olvera, Rene L.
Ophoff, Roel A.
Pandolfo, Massimo
Paus, Tomas
Pausova, Zdenka
Penninx, Brenda W. J. H.
Pike, G. Bruce
Potkin, Steven G.
Psaty, Bruce M.
Reppermund, Simone
Rietschel, Marcella
Roffman, Joshua L.
Romanczuk-Seiferth, Nina
Rotter, Jerome I.
Ryten, Mina
Sacco, Ralph L.
Sachdev, Perminder S.
Saykin, Andrew J.
Schmidt, Reinhold
Schmidt, Helena
Schofield, Peter R.
Sigursson, Sigurdur
Simmons, Andrew
Singleton, Andrew
Sisodiya, Sanjay M.
Smith, Colin
Smoller, Jordan W.
Soininen, Hilkka
Steen, Vidar M.
Stott, David J.
Sussmann, Jessika E.
Thalamuthu, Anbupalam
Toga, Arthur W.
Traynor, Bryan J.
Troncoso, Juan
Tsolaki, Magda
Tzourio, Christophe
Uitterlinden, Andre G.
Hernandez, Maria C. Valdes
Van Der Brug, Marcel
Van Der Lugt, Aad
Van Der Wee, Nic J. A.
Van Haren, Neeltje E. M.
Van 'T Ent, Dennis
Van Tol, Marie-Jose
Vardarajan, Badri N.
Vellas, Bruno
Veltman, Dick J.
Volzke, Henry
Walter, Henrik
Wardlaw, Joanna M.
Wassink, Thomas H.
Weale, Michael E.
Weinberger, Daniel R.
Weiner, Michael W.
Wen, Wei
Westman, Eric
White, Tonya
Wong, Tien Y.
Wright, Clinton B.
Zielke, Ronald H.
Zonderman, Alan B.
Martin, Nicholas G.
Van Duijn, Cornelia M.
Wright, Margaret J.
Longstreth, W. T.
Schumann, Gunter
Grabe, Hans J.
Franke, Barbara
Launer, Lenore J.
Medland, Sarah E.
Seshadri, Sudha
Thompson, Paul M.
Ikram, M. Arfan
Title Novel genetic loci associated with hippocampal volume
Journal name Nature Communications   Check publisher's open access policy
ISSN 2041-1723
Publication date 2017-01-18
Year available 2017
Sub-type Article (original research)
DOI 10.1038/ncomms13624
Open Access Status DOI
Volume 8
Start page 13624
End page 13624
Total pages 12
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Subject 1600 Chemistry
1300 Biochemistry, Genetics and Molecular Biology
3100 Physics and Astronomy
Abstract The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
Formatted abstract
The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
Keyword Multidisciplinary Sciences
Science & Technology - Other Topics
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID MC_UU_12013/2
UL1 TR001863
R01 HL105756
RF1 AG015819
U54 EB020403
K01 MH099232
T32 NS048004
104036
Institutional Status UQ

 
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