Browsing by Author "Teumer, Alexander"

Now showing 1 - 9 of 9
  • Thumbnail Image
    Item
    Common genetic variants influence human subcortical brain structures
    (Nature Publishing Group, 2015-04-09) Hibar, Derrek P.; Stein, Jason L.; Renteria, Miguel E.; Arias-Vasquez, Alejandro; Desrivières, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S.; Armstrong, Nicola J.; Bernard, Manon; Bohlken, Marc M.; Boks, Marco P.; Bralten, Janita; Brown, Andrew A.; Chakravarty, M. Mallar; Chen, Qiang; Ching, Christopher R. K.; Cuellar-Partida, Gabriel; den Braber, Anouk; Giddaluru, Sudheer; Goldman, Aaron L.; Grimm, Oliver; Guadalupe, Tulio; Hass, Johanna; Woldehawariat, Girma; Holmes, Avram J.; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H.; Olde Loohuis, Loes M.; Luciano, Michelle; Macare, Christine; Mather, Karen A.; Mattheisen, Manuel; Milaneschi, Yuri; Nho, Kwangsik; Papmeyer, Martina; Ramasamy, Adaikalavan; Risacher, Shannon L.; Roiz-Santiañez, Roberto; Rose, Emma J.; Salami, Alireza; Sämann, Philipp G.; Schmaal, Lianne; Schork, Andrew J.; Shin, Jean; Strike, Lachlan T.; Teumer, Alexander; van Donkelaar, Marjolein M. J.; van Eijk, Kristel R.; Walters, Raymond K.; Westlye, Lars T.; Whelan, Christopher D.; Winkler, Anderson M.; Zwiers, Marcel P.; Alhusaini, Saud; Athanasiu, Lavinia; Ehrlich, Stefan; Hakobjan, Marina M. H.; Hartberg, Cecilie B.; Haukvik, Unn K.; Heister, Angelien J. G. A. M.; Hoehn, David; Kasperaviciute, Dalia; Liewald, David C. M.; Lopez, Lorna M.; Makkinje, Remco R. R.; Matarin, Mar; Naber, Marlies A. M.; McKay, D. Reese; Needham, Margaret; Nugent, Allison C.; Pütz, Benno; Royle, Natalie A.; Shen, Li; Sprooten, Emma; Trabzuni, Daniah; van der Marel, Saskia S. L.; van Hulzen, Kimm J. E.; Walton, Esther; Wolf, Christiane; Almasy, Laura; Ames, David; Arepalli, Sampath; Assareh, Amelia A.; Bastin, Mark E.; Brodaty, Henry; Bulayeva, Kazima B.; Carless, Melanie A.; Cichon, Sven; Corvin, Aiden; Curran, Joanne E.; Czisch, Michael; de Zubicaray, Greig I.; Dillman, Allissa; Duggirala, Ravi; Dyer, Thomas D.; Erk, Susanne; Fedko, Iryna O.; Ferrucci, Luigi; Foroud, Tatiana M.; Fox, Peter T.; Fukunaga, Masaki; Gibbs, J. Raphael; Göring, Harald H. H.; Green, Robert C.; Guelfi, Sebastian; Hansell, Narelle K.; Hartman, Catharina A.; Hegenscheid, Katrin; Heinz, Andreas; Hernandez, Dena G.; Heslenfeld, Dirk J.; Hoekstra, Pieter J.; Holsboer, Florian; Homuth, Georg; Hottenga, Jouke-Jan; Ikeda, Masashi; Jack, Clifford R.; Jenkinson, Mark; Johnson, Robert; Kanai, Ryota; Keil, Maria; Kent, Jack W.; Kochunov, Peter; Kwok, John B.; Lawrie, Stephen M.; Liu, Xinmin; Longo, Dan L.; McMahon, Katie L.; Meisenzahl, Eva; Melle, Ingrid; Mohnke, Sebastian; Montgomery, Grant W.; Mostert, Jeanette C.; Mühleisen, Thomas W.; Nalls, Michael A.; Nichols, Thomas E.; Nilsson, Lars G.; Nöthen, Markus M.; Ohi, Kazutaka; Olvera, Rene L.; Perez-Iglesias, Rocio; Pike, G. Bruce; Potkin, Steven G.; Reinvang, Ivar; Reppermund, Simone; Rietschel, Marcella; Romanczuk-Seiferth, Nina; Rosen, Glenn D.; Rujescu, Dan; Schnell, Knut; Schofield, Peter R.; Smith, Colin; Steen, Vidar M.; Sussmann, Jessika E.; Thalamuthu, Anbupalam; Toga, Arthur W.; Traynor, Bryan J.; Troncoso, Juan; Turner, Jessica A.; Valdés Hernández, Maria C.; van ’t Ent, Dennis; van der Brug, Marcel; van der Wee, Nic J. A.; van Tol, Marie-Jose; Veltman, Dick J.; Wassink, Thomas H.; Westman, Eric; Zielke, Ronald H.; Zonderman, Alan B.; Ashbrook, David G.; Hager, Reinmar; Lu, Lu; McMahon, Francis J.; Morris, Derek W.; Williams, Robert W.; Brunner, Han G.; Buckner, Randy L.; Buitelaar, Jan K.; Cahn, Wiepke; Calhoun, Vince D.; Cavalleri, Gianpiero L.; Crespo-Facorro, Benedicto; Dale, Anders M.; Davies, Gareth E.; Delanty, Norman; Depondt, Chantal; Djurovic, Srdjan; Drevets, Wayne C.; Espeseth, Thomas; Gollub, Randy L.; Ho, Beng-Choon; Hoffmann, Wolfgang; Hosten, Norbert; Kahn, René S.; Le Hellard, Stephanie; Meyer-Lindenberg, Andreas; Müller-Myhsok, Bertram; Nauck, Matthias; Nyberg, Lars; Pandolfo, Massimo; Penninx, Brenda W. J. H.; Roffman, Joshua L.; Sisodiya, Sanjay M.; Smoller, Jordan W.; van Bokhoven, Hans; van Haren, Neeltje E. M.; Völzke, Henry; Walter, Henrik; Weiner, Michael W.; Wen, Wei; White, Tonya; Agartz, Ingrid; Andreassen, Ole A.; Blangero, John; Boomsma, Dorret I.; Brouwer, Rachel M.; Cannon, Dara M.; Cookson, Mark R.; de Geus, Eco J. C.; Deary, Ian J.; Donohoe, Gary; Fernández, Guillén; Fisher, Simon E.; Francks, Clyde; Glahn, David C.; Grabe, Hans J.; Gruber, Oliver; Hardy, John; Hashimoto, Ryota; Hulshoff Pol, Hilleke E.; Jönsson, Erik G.; Kloszewska, Iwona; Lovestone, Simon; Mattay, Venkata S.; Mecocci, Patrizia; McDonald, Colm; McIntosh, Andrew M.; Ophoff, Roel A.; Paus, Tomas; Pausova, Zdenka; Ryten, Mina; Sachdev, Perminder S.; Saykin, Andrew J.; Simmons, Andy; Singleton, Andrew; Soininen, Hilkka; Wardlaw, Joanna M.; Weale, Michael E.; Weinberger, Daniel R.; Adams, Hieab H. H.; Launer, Lenore J.; Seiler, Stephan; Schmidt, Reinhold; Chauhan, Ganesh; Satizabal, Claudia L.; Becker, James T.; Yanek, Lisa; van der Lee, Sven J.; Ebling, Maritza; Fischl, Bruce; Longstreth, W. T.; Greve, Douglas; Schmidt, Helena; Nyquist, Paul; Vinke, Louis N.; van Duijn, Cornelia M.; Xue, Luting; Mazoyer, Bernard; Bis, Joshua C.; Gudnason, Vilmundur; Seshadri, Sudha; Ikram, M. Arfan; Martin, Nicholas G.; Wright, Margaret J.; Schumann, Gunter; Franke, Barbara; Thompson, Paul M.; Medland, Sarah E.; Department of Radiology and Imaging Sciences, IU School of Medicine
    The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270
  • Thumbnail Image
    Item
    Genetic architecture of subcortical brain structures in 38,851 individuals
    (Nature, 2019-11) Satizabal, Claudia L.; Adams, Hieab H. H.; Hibar, Derrek P.; White, Charles C.; Knol, Maria J.; Stein, Jason L.; Scholz, Markus; Sargurupremraj, Muralidharan; Jahanshad, Neda; Roshchupkin, Gennady V.; Smith, Albert V.; Bis, Joshua C.; Jian, Xueqiu; Luciano, Michelle; Hofer, Edith; Teumer, Alexander; van der Lee, Sven J.; Yang, Jingyun; Yanek, Lisa R.; Lee, Tom V.; Li, Shuo; Hu, Yanhui; Koh, Jia Yu; Eicher, John D.; Desrivières, Sylvane; Arias-Vasquez, Alejandro; Chauhan, Ganesh; Athanasiu, Lavinia; Rentería, Miguel E.; Kim, Sungeun; Hoehn, David; Armstrong, Nicola J.; Chen, Qiang; Holmes, Avram J.; den Braber, Anouk; Kloszewska, Iwona; Andersson, Micael; Espeseth, Thomas; Grimm, Oliver; Abramovic, Lucija; Alhusaini, Saud; Milaneschi, Yuri; Papmeyer, Martina; Axelsson, Tomas; Ehrlich, Stefan; Roiz-Santiañez, Roberto; Kraemer, Bernd; Håberg, Asta K.; Jones, Hannah J.; Pike, G. Bruce; Stein, Dan J.; Stevens, Allison; Bralten, Janita; Vernooij, Meike W.; Harris, Tamara B.; Filippi, Irina; Witte, A. Veronica; Guadalupe, Tulio; Wittfeld, Katharina; Mosley, Thomas H.; Becker, James T.; Doan, Nhat Trung; Hagenaars, Saskia P.; Saba, Yasaman; Cuellar-Partida, Gabriel; Amin, Najaf; Hilal, Saima; Nho, Kwangsik; Mirza-Schreiber, Nazanin; Arfanakis, Konstantinos; Becker, Diane M.; Ames, David; Goldman, Aaron L.; Lee, Phil H.; Boomsma, Dorret I.; Lovestone, Simon; Giddaluru, Sudheer; Le Hellard, Stephanie; Mattheisen, Manuel; Bohlken, Marc M.; Kasperaviciute, Dalia; Schmaal, Lianne; Lawrie, Stephen M.; Agartz, Ingrid; Walton, Esther; Tordesillas-Gutierrez, Diana; Davies, Gareth E.; Shin, Jean; Ipser, Jonathan C.; Vinke, Louis N.; Hoogman, Martine; Jia, Tianye; Burkhardt, Ralph; Klein, Marieke; Crivello, Fabrice; Janowitz, Deborah; Carmichael, Owen; Haukvik, Unn K.; Aribisala, Benjamin S.; Schmidt, Helena; Strike, Lachlan T.; Cheng, Ching-Yu; Risacher, Shannon L.; Pütz, Benno; Fleischman, Debra A.; Assareh, Amelia A.; Mattay, Venkata S.; Buckner, Randy L.; Mecocci, Patrizia; Dale, Anders M.; Cichon, Sven; Boks, Marco P.; Matarin, Mar; Penninx, Brenda W. J. H.; Calhoun, Vince D.; Chakravarty, M. Mallar; Marquand, Andre F.; Macare, Christine; Kharabian Masouleh, Shahrzad; Oosterlaan, Jaap; Amouyel, Philippe; Hegenscheid, Katrin; Rotter, Jerome I.; Schork, Andrew J.; Liewald, David C. M.; de Zubicaray, Greig I.; Wong, Tien Yin; Shen, Li; Sämann, Philipp G.; Brodaty, Henry; Roffman, Joshua L.; de Geus, Eco J. C.; Tsolaki, Magda; Erk, Susanne; van Eijk, Kristel R.; Cavalleri, Gianpiero L.; van der Wee, Nic J. A.; McIntosh, Andrew M.; Gollub, Randy L.; Bulayeva, Kazima B.; Bernard, Manon; Richards, Jennifer S.; Himali, Jayandra J.; Loeffler, Markus; Rommelse, Nanda; Hoffmann, Wolfgang; Westlye, Lars T.; Valdés Hernández, Maria C.; Hansell, Narelle K.; van Erp, Theo G. M.; Wolf, Christiane; Kwok, John B. J.; Vellas, Bruno; Heinz, Andreas; Olde Loohuis, Loes M.; Delanty, Norman; Ho, Beng-Choon; Ching, Christopher R. K.; Shumskaya, Elena; Singh, Baljeet; Hofman, Albert; van der Meer, Dennis; Homuth, Georg; Psaty, Bruce M.; Bastin, Mark E.; Montgomery, Grant W.; Foroud, Tatiana M.; Reppermund, Simone; Hottenga, Jouke-Jan; Simmons, Andrew; Meyer-Lindenberg, Andreas; Cahn, Wiepke; Whelan, Christopher D.; van Donkelaar, Marjolein M. J.; Yang, Qiong; Hosten, Norbert; Green, Robert C; Thalamuthu, Anbupalam; Mohnke, Sebastian; Hulshoff Pol, Hilleke E.; Lin, Honghuang; Jack, Clifford R.; Schofield, Peter R.; Mühleisen, Thomas W.; Maillard, Pauline; Potkin, Steven G.; Wen, Wei; Fletcher, Evan; Toga, Arthur W.; Gruber, Oliver; Huentelman, Matthew; Davey Smith, George; Launer, Lenore J.; Nyberg, Lars; Jönsson, Erik G.; Crespo-Facorro, Benedicto; Koen, Nastassja; Greve, Douglas N.; Uitterlinden, André G.; Weinberger, Daniel R.; Steen, Vidar M.; Fedko, Iryna O.; Groenewold, Nynke A.; Niessen, Wiro J.; Toro, Roberto; Tzourio, Christophe; Longstreth, William T.; Ikram, M. Kamran; Smoller, Jordan W.; van Tol, Marie-Jose; Sussmann, Jessika E.; Paus, Tomas; Lemaître, Hervé; Schroeter, Matthias L.; Mazoyer, Bernard; Andreassen, Ole A.; Holsboer, Florian; Depondt, Chantal; Veltman, Dick J.; Turner, Jessica A.; Pausova, Zdenka; Schumann, Gunter; van Rooij, Daan; Djurovic, Srdjan; Deary, Ian J.; McMahon, Katie L.; Müller-Myhsok, Bertram; Brouwer, Rachel M.; Soininen, Hilkka; Pandolfo, Massimo; Wassink, Thomas H.; Cheung, Joshua W.; Wolfers, Thomas; Martinot, Jean-Luc; Zwiers, Marcel P.; Nauck, Matthias; Melle, Ingrid; Martin, Nicholas G.; Kanai, Ryota; Westman, Eric; Kahn, René S.; Sisodiya, Sanjay M.; White, Tonya; Saremi, Arvin; van Bokhoven, Hans; Brunner, Han G.; Völzke, Henry; Wright, Margaret J.; van ‘t Ent, Dennis; Nöthen, Markus M.; Ophoff, Roel A.; Buitelaar, Jan K.; Fernández, Guillén; Sachdev, Perminder S.; Rietschel, Marcella; van Haren, Neeltje E. M.; Fisher, Simon E.; Beiser, Alexa S.; Francks, Clyde; Saykin, Andrew J.; Mather, Karen A.; Romanczuk-Seiferth, Nina; Hartman, Catharina A.; DeStefano, Anita L.; Heslenfeld, Dirk J.; Weiner, Michael W.; Walter, Henrik; Hoekstra, Pieter J.; Nyquist, Paul A.; Franke, Barbara; Bennett, David A.; Grabe, Hans J.; Johnson, Andrew D.; Chen, Christopher; van Duijn, Cornelia M.; Lopez, Oscar L.; Fornage, Myriam; Wardlaw, Joanna M.; Schmidt, Reinhold; DeCarli, Charles; De Jager, Philip L.; Villringer, Arno; Debette, Stéphanie; Gudnason, Vilmundur; Medland, Sarah E.; Shulman, Joshua M.; Thompson, Paul M.; Seshadri, Sudha; Ikram, M. Arfan; Medical and Molecular Genetics, School of Medicine
    Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
  • Thumbnail Image
    Item
    The Genetic Architecture of the Human Cerebral Cortex
    (American Association for the Advancement of Science, 2020-03-20) Grasby, Katrina L.; Jahanshad, Neda; Painter, Jodie N.; Colodro-Conde, Lucía; Bralten, Janita; Hibar, Derrek P.; Lind, Penelope A.; Pizzagalli, Fabrizio; Ching, Christopher R.K.; McMahon, Mary Agnes B.; Shatokhina, Natalia; Zsembik, Leo C.P.; Thomopoulos, Sophia I.; Zhu, Alyssa H.; Strike, Lachlan T.; Agartz, Ingrid; Alhusaini, Saud; Almeida, Marcio A.A.; Alnæs, Dag; Amlien, Inge K.; Andersson, Micael; Ard, Tyler; Armstrong, Nicola J.; Ashley-Koch, Allison; Atkins, Joshua R.; Bernard, Manon; Brouwer, Rachel M.; Buimer, Elizabeth E.L.; Bülow, Robin; Bürger, Christian; Cannon, Dara M.; Chakravarty, Mallar; Chen, Qiang; Cheung, Joshua W.; Couvy-Duchesne, Baptiste; Dale, Anders M.; Dalvie, Shareefa; de Araujo, Tânia K.; de Zubicaray, Greig I.; de Zwarte, Sonja M.C.; den Braber, Anouk; Doan, Nhat Trung; Dohm, Katharina; Ehrlich, Stefan; Engelbrecht, Hannah-Ruth; Erk, Susanne; Fan, Chun Chieh; Fedko, Iryna O.; Foley, Sonya F.; Ford, Judith M.; Fukunaga, Masaki; Garrett, Melanie E.; Ge, Tian; Giddaluru, Sudheer; Goldman, Aaron L.; Green, Melissa J.; Groenewold, Nynke A.; Grotegerd, Dominik; Gurholt, Tiril P.; Gutman, Boris A.; Hansell, Narelle K.; Harris, Mathew A.; Harrison, Marc B.; Haswell, Courtney C.; Hauser, Michael; Herms, Stefan; Heslenfeld, Dirk J.; Ho, New Fei; Hoehn, David; Hoffmann, Per; Holleran, Laurena; Hoogman, Martine; Hottenga, Jouke-Jan; Ikeda, Masashi; Janowitz, Deborah; Jansen, Iris E.; Jia, Tianye; Jockwitz, Christiane; Kanai, Ryota; Karama, Sherif; Kasperaviciute, Dalia; Kaufmann, Tobias; Kelly, Sinead; Kikuchi, Masataka; Klein, Marieke; Knapp, Michael; Knodt, Annchen R.; Krämer, Bernd; Lam, Max; Lancaster, Thomas M.; Lee, Phil H.; Lett, Tristram A.; Lewis, Lindsay B.; Lopes-Cendes, Iscia; Luciano, Michelle; Macciardi, Fabio; Marquand, Andre F.; Mathias, Samuel R.; Melzer, Tracy R.; Milaneschi, Yuri; Mirza-Schreiber, Nazanin; Moreira, Jose C.V.; Mühleisen, Thomas W.; Müller-Myhsok, Bertram; Najt, Pablo; Nakahara, Soichiro; Nho, Kwangsik; lde Loohuis, Loes M.O.; Orfanos, Dimitri Papadopoulos; Pearson, John F.; Pitcher, Toni L.; Pütz, Benno; Quidé, Yann; Ragothaman, Anjanibhargavi; Rashid, Faisal M.; Reay, William R.; Redlich, Ronny; Reinbold, Céline S.; Repple, Jonathan; Richard, Geneviève; Riedel, Brandalyn C.; Risacher, Shannon L.; Rocha, Cristiane S.; Roth Mota, Nina; Salminen, Lauren; Saremi, Arvin; Saykin, Andrew J.; Schlag, Fenja; Schmaal, Lianne; Schofield, Peter R.; Secolin, Rodrigo; Shapland, Chin Yang; Shen, Li; Shin, Jean; Shumskaya, Elena; Sønderby, Ida E.; Sprooten, Emma; Tansey, Katherine E.; Teumer, Alexander; Thalamuthu, Anbupalam; Tordesillas-Gutiérrez, Diana; Turner, Jessica A.; Uhlmann, Anne; Vallerga, Costanza Ludovica; van der Meer, Dennis; van Donkelaar, Marjolein M.J.; van Eijk, Liza; van Erp, Theo G.M.; van Haren, Neeltje E.M.; van Rooij, Daan; van Tol, Marie-José; Veldink, Jan H.; Verhoef, Ellen; Walton, Esther; Wang, Mingyuan; Wang, Yunpeng; Wardlaw, Joanna M.; Wen, Wei; Westlye, Lars T.; Whelan, Christopher D.; Witt, Stephanie H.; Wittfeld, Katharina; Wolf, Christiane; Wolfers, Thomas; Wu, Jing Qin; Yasuda, Clarissa L.; Zaremba, Dario; Zhang, Zuo; Zwiers, Marcel P.; Artiges, Eric; Assareh, Amelia A.; Ayesa-Arriol, Rosa; Belger, Aysenil; Brandt, Christine L.; Brown, Gregory G.; Cichon, Sven; Curran, Joanne E.; Davies, Gareth E.; Degenhard, Franziska; Dennis, Michelle F.; Dietsche, Bruno; Djurovic, Srdjan; Doherty, Colin P.; Espiritu, Ryan; Garijo, Daniel; Gil, Yolanda; Gowland, Penny A.; Green, Robert C.; Häusler, Alexander N.; Heindel, Walter; Ho, Beng-Choon; Hoffmann, Wolfgang U.; Holsboer, Florian; Homuth, Georg; Hosten, Norbert; Jack, Clifford R.,Jr.; Jang, MiHyun; Jansen, Andreas; Kimbrel, Nathan A.; Kolskår, Knut; Koops, Sanne; Krug, Axel; Lim, Kelvin O.; Luykx, Jurjen J.; Mathalon, Daniel H.; Mather, Karen A.; Mattay, Venkata S.; Matthews, Sarah; Mayoral Van Son, Jaqueline; McEwen, Sarah C.; Melle, Ingrid; Morris, Derek W.; Mueller, Bryon A.; Nauck, Matthias; Nordvik, Jan E.; Nöthen, Markus M.; O'Leary, Daniel S.; Opel, Nils; Paillère Martinot, Marie-Laure; Pike, G. Bruce; Preda, Adrian; Quinlan, Erin B.; Rasser, Paul E.; Ratnakar, Varun; Reppermund, Simone; Steen, Vidar M.; Tooney, Paul A.; Torres, Fábio R.; Veltman, Dick J.; Voyvodic, James T.; Whelan, Robert; White, Tonya; Yamamori, Hidenaga; Adams, Hieab H.H.; Bis, Joshua C.; Debette, Stephanie; Decarli, Charles; Fornage, Myriam; Gudnason, Vilmundur; Hofer, Edith; Ikram, M. Arfan; Launer, Lenore; Longstreth, W.T.; Lopez, Oscar L.; Mazoyer, Bernard; Mosley, Thomas H.; Roshchupkin, Gennady V.; Satizabal, Claudia L.; Schmidt, Reinhold; Seshadri, Sudha; Yang, Qiong; Alvim, Marina K.M.; Ames, David; Anderson, Tim J.; Andreassen, Ole A.; Arias-Vasquez, Alejandro; Bastin, Mark E.; Baune, Bernhard T.; Beckham, Jean C.; Blangero, John; Boomsma, Dorret I.; Brodaty, Henry; Brunner, Han G.; Buckner, Randy L.; Buitelaar, Jan K.; Bustillo, Juan R.; Cahn, Wiepke; Cairns, Murray J.; Calhoun, Vince; Carr, Vaughan J.; Caseras, Xavier; Caspers, Svenja; Cavalleri, Gianpiero L.; Cendes, Fernando; Corvin, Aiden; Crespo-Facorro, Benedicto; Dalrymple-Alford, John C.; Dannlowski, Udo; de Geus, Eco J.C.; Deary, Ian J.; Delanty, Norman; Depondt, Chantal; Desrivières, Sylvane; Donohoe, Gary; Espeseth, Thomas; Fernández, Guillén; Fisher, Simon E.; Flor, Herta; Forstner, Andreas J.; Francks, Clyde; Franke, Barbara; Glahn, David C.; Gollub, Randy L.; Grabe, Hans J.; Gruber, Oliver; Håberg, Asta K.; Hariri, Ahmad R.; Hartman, Catharina A.; Hashimoto, Ryota; Heinz, Andreas; Henskens, Frans A.; Hillegers, Manon H.J.; Hoekstra, Pieter J.; Holmes, Avram J.; Hong, L. Elliot; Hopkins, William D.; Hulshoff Pol, Hilleke E.; Jernigan, Terry L.; Jönsson, Erik G.; Kahn, René S.; Kennedy, Martin A.; Kircher, Tilo T.J.; Kochunov, Peter; Kwok, John B.J.; Le Hellard, Stephanie; Loughland, Carmel M.; Martin, Nicholas G.; Martinot, Jean-Luc; McDonald, Colm; McMahon, Katie L.; Meyer-Lindenberg, Andreas; Michie, Patricia T.; Morey, Rajendra A.; Mowry, Bryan; Nyberg, Lars; Oosterlaan, Jaap; Ophoff, Roel A.; Pantelis, Christos; Paus, Tomas; Pausova, Zdenka; Penninx, Brenda W.J.H.; Polderman, Tinca J.C.; Posthuma, Danielle; Rietschel, Marcella; Roffman, Joshua L.; Rowland, Laura M.; Sachdev, Perminder S.; Sämann, Philipp G.; Schall, Ulrich; Schumann, Gunter; Scott, Rodney J.; Sim, Kang; Sisodiya, Sanjay M.; Smoller, Jordan W.; Sommer, Iris E.; St. Pourcain, Beate; Stein, Dan J.; Toga, Arthur W.; Trollor, Julian N.; Van der Wee, Nic J.A.; van't Ent, Dennis; Völzke, Henry; Walter, Henrik; Weber, Bernd; Weinberger, Daniel R.; Wright, Margaret J.; Zhou, Juan; Stein, Jason L.; Thompson, Paul M.; Medland, Sarah E.; Radiology and Imaging Sciences, School of Medicine
    The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.
  • Thumbnail Image
    Item
    Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning
    (Springer Nature, 2022) Lahti, Jari; Tuominen, Samuli; Yang, Qiong; Pergola, Giulio; Ahmad, Shahzad; Amin, Najaf; Armstrong, Nicola J.; Beiser, Alexa; Bey, Katharina; Bis, Joshua C.; Boerwinkle, Eric; Bressler, Jan; Campbell, Archie; Campbell, Harry; Chen, Qiang; Corley, Janie; Cox, Simon R.; Davies, Gail; De Jager, Philip L.; Derks, Eske M.; Faul, Jessica D.; Fitzpatrick, Annette L.; Fohner, Alison E.; Ford, Ian; Fornage, Myriam; Gerring, Zachary; Grabe, Hans J.; Grodstein, Francine; Gudnason, Vilmundur; Simonsick, Eleanor; Holliday, Elizabeth G.; Joshi, Peter K.; Kajantie, Eero; Kaprio, Jaakko; Karell, Pauliina; Kleineidam, Luca; Knol, Maria J.; Kochan, Nicole A.; Kwok, John B.; Leber, Markus; Lam, Max; Lee, Teresa; Li, Shuo; Loukola, Anu; Luck, Tobias; Marioni, Riccardo E.; Mather, Karen A.; Medland, Sarah; Mirza, Saira S.; Nalls, Mike A.; Nho, Kwangsik; O'Donnell, Adrienne; Oldmeadow, Christopher; Painter, Jodie; Pattie, Alison; Reppermund, Simone; Risacher, Shannon L.; Rose, Richard J.; Sadashivaiah, Vijay; Scholz, Markus; Satizabal, Claudia L.; Schofield, Peter W.; Schraut, Katharina E.; Scott, Rodney J.; Simino, Jeannette; Smith, Albert V.; Smith, Jennifer A.; Stott, David J.; Surakka, Ida; Teumer, Alexander; Thalamuthu, Anbupalam; Trompet, Stella; Turner, Stephen T.; van der Lee, Sven J.; Villringer, Arno; Völker, Uwe; Wilson, Robert S.; Wittfeld, Katharina; Vuoksimaa, Eero; Xia, Rui; Yaffe, Kristine; Yu, Lei; Zare, Habil; Zhao, Wei; Ames, David; Attia, John; Bennett, David A.; Brodaty, Henry; Chasman, Daniel I.; Goldman, Aaron L.; Hayward, Caroline; Ikram, M. Arfan; Jukema, J. Wouter; Kardia, Sharon L.R.; Lencz, Todd; Loeffler, Markus; Mattay, Venkata S.; Palotie, Aarno; Psaty, Bruce M.; Ramirez, Alfredo; Ridker, Paul M.; Riedel-Heller, Steffi G.; Sachdev, Perminder S.; Saykin, Andrew J.; Scherer, Martin; Schofield, Peter R.; Sidney, Stephen; Starr, John M.; Trollor, Julian; Ulrich, William; Wagner, Michael; Weir, David R.; Wilson, James F.; Wright, Margaret J.; Weinberger, Daniel R.; Debette, Stephanie; Eriksson, Johan G.; Mosley, Thomas H., Jr.; Launer, Lenore J.; van Duijn, Cornelia M.; Deary, Ian J.; Seshadri, Sudha; Räikkönen, Katri; Radiology and Imaging Sciences, School of Medicine
    Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent sample. Functional and bioinformatic analyses supported many of these loci and further implicated POC1. We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during working memory task. Finally, we showed genetic correlations of these memory traits with several neurocognitive and health outcomes. Our findings suggest a role of several genomic loci in verbal memory processes.
  • Thumbnail Image
    Item
    Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk
    (Nature, 2017) Day, Felix R.; Thompson, Deborah J.; Helgason, Hannes; Chasman, Daniel I.; Finucane, Hilary; Sulem, Patrick; Ruth, Katherine S.; Whalen, Sean; Sarkar, Abhishek K.; Albrecht, Eva; Altmaier, Elisabeth; Amini, Marzyeh; Barbieri, Caterina M.; Boutin, Thibaud; Campbell, Archie; Demerath, Ellen; Giri, Ayush; He, Chunyan; Hottenga, Jouke J.; Karlsson, Robert; Kolchic, Ivana; Loh, Po-Ru; Lunetta, Kathryn L.; Mangino, Massimo; Marco, Brumat; McMahon, George; Medland, Sarah E.; Nolte, Ilja M.; Noordam, Raymond; Nutile, Teresa; Paternoster, Lavinia; Perjakova, Natalia; Porcu, Eleonora; Rose, Lynda M.; Schraut, Katharina E.; Segrè, Ayellet V.; Smith, Albert V.; Stolk, Lisette; Teumer, Alexander; Andrulis, Irene L.; Bandinelli, Stefania; Beckmann, Matthias W.; Benitez, Javier; Bergmann, Sven; Bochud, Murielle; Boerwinkle, Eric; Bojesen, Stig E.; Bolla, Manjeet K.; Brand, Judith S.; Brauch, Hiltrud; Brenner, Hermann; Broer, Linda; Brüning, Thomas; Buring, Julie E.; Campbell, Harry; Catamo, Eulalia; Chanock, Stephen; Chenevix-Trench, Georgia; Corre, Tanguy; Couch, Fergus J.; Cousminer, Diana L.; Cox, Angela; Crisponi, Laura; Czene, Kamila; Davey-Smith, George; de Geus, Eco J. C. N.; de Mutsert, Renée; De Vivo, Immaculata; Dennis, Joe; Devilee, Peter; dos-Santos-Silva, Isabel; Dunning, Alison M.; Eriksson, Johan G.; Fasching, Peter A.; Fernández-Rhodes, Lindsay; Ferrucci, Luigi; Flesch-Janys, Dieter; Franke, Lude; Gabrielson, Marike; Gandin, Ilaria; Giles, Graham G.; Grallert, Harald; Gudbjartsson, Daniel F.; Guéne, Pascal; Hall, Perr; Hallberg, Emily; Hamann, Ute; Harris, Tamara B.; Hartman, Catharina A.; Heiss, Gerardo; Hooning, Maartje J.; Hopper, John L.; Hu, Frank; Hunter, David; Ikram, M. Arfan; Im, Hae Kyung; Järvelin, Marjo-Riitta; Joshi, Peter K.; Karasik, David; Kutalik, Zoltan; LaChance, Genevieve; Lambrechts, Diether; Langenberg, Claudia; Launer, Lenore J.; Laven, Joop S. E.; Lenarduzzi, Stefania; Li, Jingmei; Lind, Penelope A.; Lindstrom, Sara; Liu, YongMei; Luan, Jian'an; Mannermaa, Arto; Mbarek, Hamdi; McCarthy, Mark I.; Meisinger, Christa; Meitinger, Thomas; Menni, Cristina; Metspalu, Andres; Michailidou, Kyriaki; Milani, Lili; Milne, Roger L.; Montgomery, Grant W.; Mulligan, Anna M.; Nalls, Mike A.; Navarro, Pau; Nevanlinna, Heli; Nyholt, Dale R.; Oldehinkel, Albertine J.; O'Mara, Tracy A.; Padmanabhan, Sandosh; Palotie, Aarno; Pedersen, Nancy; Peters, Annette; Peto, Julian; Pharoah, Paul D. P.; Pouta, Anneli; Radice, Paolo; Rahman, Iffat; Ring, Susan M.; Robino, Antonietta; Rosendaal, Frits R.; Rudan, Igor; Rueedi, Rico; Ruggiero, Daniela; Sala, Cinzia F.; Schmidt, Marjanka K.; Scott, Robert A.; Shah, Mitul; Sorice, Rossella; Southey, Melissa C.; Sovio, Ulla; Stampfer, Meir; Steri, Maristella; Strauch, Konstantin; Tanaka, Toshiko; Tikkanen, Emmi; Timpson, Nicholas J.; Traglia, Michela; Truong, Thérèse; Tyrer, Jonathan P.; Uitterlinden, André G.; Edwards, Digna R. Velez; Vitart, Veronique; Völker, Uwe; Vollenweider, Peter; Wang, Qin; Widen, Elisabeth; van Dijk, Ko Willems; Willemsen, Gonneke; Winqvist, Robert; Wolffenbuttel, Bruce H. R.; Zhao, Jing Hua; Zoledziewska, Magdalena; Zygmunt, Marek; Alizadeh, Behrooz Z.; Boomsma, Dorret I.; Ciullo, Marina; Cucca, Francesco; Esko, Tõnu; Franceschini, Nora; Gieger, Christian; Gudnason, Vilmundur; Hayward, Caroline; Kraft, Peter; Lawlor, Debbie A.; Magnusson, Patrik K. E.; Martin, Nicholas G.; Mook-Kanamori, Dennis O.; Nohr, Ellen A.; Polasek, Ozren; Porteous, David; Price, Alkes L.; Ridker, Paul M.; Snieder, Harold; Spector, Tim D.; Stöckl, Doris; Toniolo, Daniela; Ulivi, Sheila; Visser, Jenny A.; Völzke, Henry; Wareham, Nicholas J.; Wilson, James F.; Spurdle, Amanda B.; Thorsteindottir, Unnur; Pollard, Katherine S.; Easton, Douglas F.; Tung, Joyce Y.; Chang-Claude, Jenny; Hinds, David; Murray, Anna; Murabito, Joanne M.; Stefansson, Kari; Ong, Ken K.; Perry, John R. B.; The Lifelines Cohort Study; The InterAct Consortium; kConFab/AOCS Investigators; Endometrial Cancer Association Consortium; Ovarian Cancer Association Consortium; PRACTICAL consortium; Epidemiology, School of Public Health
    The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000 Genomes Project–imputed genotype data in up to ∼370,000 women, we identify 389 independent signals (P < 5 × 10−8) for age at menarche, a milestone in female pubertal development. In Icelandic data, these signals explain ∼7.4% of the population variance in age at menarche, corresponding to ∼25% of the estimated heritability. We implicate ∼250 genes via coding variation or associated expression, demonstrating significant enrichment in neural tissues. Rare variants near the imprinted genes MKRN3 and DLK1 were identified, exhibiting large effects when paternally inherited. Mendelian randomization analyses suggest causal inverse associations, independent of body mass index (BMI), between puberty timing and risks for breast and endometrial cancers in women and prostate cancer in men. In aggregate, our findings highlight the complexity of the genetic regulation of puberty timing and support causal links with cancer susceptibility.
  • Thumbnail Image
    Item
    Large-scale genomic analyses link reproductive ageing to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair
    (SpringerNature, 2015-11) Day, Felix R.; Ruth, Katherine S.; Thompson, Deborah J.; Lunetta, Kathryn L.; Pervjakova, Natalia; Chasman, Daniel I.; Stolk, Lisette; Finucane, Hilary K.; Sulem, Patrick; Bulik-Sullivan, Brendan; Esko, Tõnu; Johnson, Andrew D.; Elks, Cathy E.; Franceschini, Nora; He, Chunyan; Altmaier, Elisabeth; Brody, Jennifer A.; Franke, Lude L.; Huffman, Jennifer E.; Keller, Margaux F.; McArdle, Patrick F.; Nutile, Teresa; Porcu, Eleonora; Robino, Antonietta; Rose, Lynda M.; Schick, Ursula M.; Smith, Jennifer A.; Teumer, Alexander; Traglia, Michela; Vuckovic, Dragana; Yao, Jie; Zhao, Wei; Albrecht, Eva; Amin, Najaf; Corre, Tanguy; Hottenga, Jouke-Jan; Mangino, Massimo; Smith, Albert V.; Tanaka, Toshiko; Abecasis, Goncalo; Andrulis, Irene L.; Anton-Culver, Hoda; Antoniou, Antonis C.; Arndt, Volker; Arnold, Alice M.; Barbieri, Caterina; Beckmann, Matthias W.; Beeghly-Fadiel, Alicia; Benitez, Javier; Bernstein, Leslie; Bielinski, Suzette J.; Blomqvist, Carl; Boerwinkle, Eric; Bogdanova, Natalia V.; Bojesen, Stig E.; Bolla, Manjeet K.; Borresen-Dale, Anne-Lise; Boutin, Thibaud S.; Brauch, Hiltrud; Brenner, Hermann; Brüning, Thomas; Burwinkel, Barbara; Campbell, Archie; Campbell, Harry; Chanock, Stephen J.; Chapman, J. Ross; Chen, Yii-Der Ida; Chenevix-Trench, Georgia; Couch, Fergus J.; Coviello, Andrea D.; Cox, Angela; Czene, Kamila; Darabi, Hatef; De Vivo, Immaculata; Demerath, Ellen W.; Dennis, Joe; Devilee, Peter; Dörk, Thilo; dos-Santos-Silva, Isabel; Dunning, Alison M.; Eicher, John D.; Fasching, Peter A.; Faul, Jessica D.; Figueroa, Jonine; Flesch-Janys, Dieter; Gandin, Ilaria; Garcia, Melissa E.; García-Closas, Montserrat; Giles, Graham G.; Girotto, Giorgia G.; Goldberg, Mark S.; González-Neira, Anna; Goodarzi, Mark O.; Grove, Megan L.; Gudbjartsson, Daniel F.; Guénel, Pascal; Guo, Xiuqing; Haiman, Christopher A.; Hall, Per; Hamann, Ute; Henderson, Brian E.; Hocking, Lynne J.; Hofman, Albert; Homuth, Georg; Hooning, Maartje J.; Hopper, John L.; Hu, Frank B.; Huang, Jinyan; Humphreys, Keith; Hunter, David J.; Jakubowska, Anna; Jones, Samuel E.; Kabisch, Maria; Karasia, David; Knight, Julia A.; Kolcic, Ivana; Kooperberg, Charles; Kosma, Veli-Matti; Kriebel, Jennifer; Kristensen, Vessela; Lambrechts, Diether; Langenberg, Claudia; Li, Jingmei; Li, Xin; Lindström, Sara; Liu, Yongmei; Luan, Jian’an; Lubinski, Jan; Mägi, Reedik; Mannermaa, Arto; Manz, Judith; Margolin, Sara; Marten, Jonathan; Martin, Nicholas G.; Masciullo, Corrado; Meindl, Alfons; Michailidou, Kyriaki; Mihailov, Evelin; Milani, Lili; Milne, Roger L.; Müller-Nurasyid, Martina; Nalls, Michael; Neale, Ben M.; Nevanlinna, Heli; Neven, Patrick; Newman, Anne B.; Nordestgaard, Børge G.; Olson, Janet E.; Padmanabhan, Sandosh; Peterlongo, Paolo; Peters, Ulrike; Petersmann, Astrid; Peto, Julian; Pharoah, Paul D.P.; Pirastu, Nicola N.; Pirie, Ailith; Pistis, Giorgio; Polasek, Ozren; Porteous, David; Psaty, Bruce M.; Pylkäs, Katri; Radice, Paolo; Raffel, Leslie J.; Rivadeneira, Fernando; Rudan, Igor; Rudolph, Anja; Anja, Daniela; Sala, Cinzia F.; Sanna, Serena; Sawyer, Elinor J.; Schlessinger, David; Schmidt, Marjanka K.; Schmidt, Frank; Schmutzler, Rita K.; Schoemaker, Minouk J.; Scott, Robert A.; Seynaeve, Caroline M.; Simard, Jacques; Sorice, Rossella; Southey, Melissa C.; Stöckl, Doris; Strauch, Konstantin; Swerdlow, Anthony; Taylor, Kent D.; Thorsteinsdottir, Unnur; Toland, Amanda E.; Tomlinson, Ian; Truong, Thérèse; Tryggvadottir, Laufey; Turner, Stephen T.; Vozzi, Diego; Wang, Qin; Wellons, Melissa; Willemsen, Gonneke; Wilson, James F.; Winqvist, Robert; Wolffenbuttel, Bruce B.H.R.; Wright, Alan F.; Yannoukakos, Drakoulis; Zemunik, Tatijana; Zheng, Wei; Zygmunt, Marek; Bergmann, Sven; Boomsma, Dorret I.; Buring, Julie E.; Ferrucci, Luigi; Montgomery, Grant W.; Gudnason, Vilmundur; Spector, Tim D.; van Duijn, Cornelia M; Alizadeh, Behrooz Z.; Ciullo, Marina; Crisponi, Laura; Easton, Douglas F.; Gasparini, Paolo P.; Gieger, Christian; Harris, Tamara B.; Hayward, Caroline; Kardia, Sharon L.R.; Kraft, Peter; McKnight, Barbara; Metspalu, Andres; Morrison, Alanna C.; Reiner, Alex P.; Ridker, Paul M.; Rotter, Jerome I.; Toniolo, Daniela; Uitterlinden, André G.; Ulivi, Sheila; Völzke, Henry; Wareham, Nicholas J.; Weir, David R.; Yerges-Armstrong, Laura M.; Price, Alkes L.; Stefansson, Kari; Visser, Jenny A.; Ong, Ken K.; Chang-Claude, Jenny; Murabito, Joanne M.; Perry, John R.B.; Murray, Anna; Department of Epidemiology, Richard M. Fairbanks School of Public Health
    Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in ∼70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two regions harboring additional rare missense alleles of large effect. We found enrichment of signals in or near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses identified major association with DNA damage response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomization analyses supported a causal effect of later ANM on breast cancer risk (∼6% increase in risk per year; P = 3 × 10(-14)), likely mediated by prolonged sex hormone exposure rather than DDR mechanisms.
  • Thumbnail Image
    Item
    Novel genetic loci associated with hippocampal volume
    (SpringerNature, 2017-01-18) 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; Desrivières, 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, 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; Jørgensen, 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; Maniega, Susana Muñoz; Nho, Kwangsik; Nugent, Allison C.; Nyquist, Paul; Loohuis, Loes M.; Oosterlaan, Jaap; Papmeyer, Martina; Pirpamer, Lukas; Pütz, Benno; Ramasamy, Adaikalavan; Richards, Jennifer S.; Risacher, Shannon L.; Roiz-Santiañez, Roberto; Rommelse, Nanda; Ropele, Stefan; Rose, Emma J.; Royle, Natalie A.; Rundek, Tatjana; Sämann, 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, Stéphanie; 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.; Fernández, Guillén; 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.; Göring, Harald H.H.; Green, Robert C.; Gruber, Oliver; Gudnason, Vilmundur; Guelfi, Sebastian; Håberg, 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-Coon; Hoekstra, Pieter J.; Hoffman, Wolfgang; Hofman, Albert; Holsboer, Florian; Homuth, Georg; Hosten, Norbert; Hottenga, Jouke-Jan; Huentelman, Matthew; Pol, Hilleke E. Hulshoff; Ikeda, Masashi; Jack Jr., Clifford R.; Jenkinson, Mark; Johnson, Robert; Jönsson, Erik G.; Jukema, J. Wouter; Kahn, René S; Vardarajan, Badri N.; Vellas, Bruno; Veltman, Dick J.; Völzke, Henry; Walter, Henrik; Wardlaw, Joanna M.; Wassink, Thomas H.; Weale, Michael E.; Weinberger, Daniel R.; Weiner, Michael W.; Kanai, Ryota; Kloszewska, Iwona; Knopman, David S.; Kochunov, Peter; Kwok, John B.; Lawrie, Stephen M.; Lemaître, Hervé; 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.; Mühleisen, Thomas W.; Müller-Myhsok, Bertram; Nalls, Michael A.; Nauck, Matthias; Nichols, Thomas E.; Niessen, Wiro J.; Nöthen, Markus M.; Nyberg, Lars; Purohit, 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.; Valdés Hernández, Maria C.; 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; 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.; Arfan, M.; Department of Radiology and Imaging Sciences, IU School of Medicine
    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.
  • Thumbnail Image
    Item
    Parent-of-origin specific allelic associations among 106 genomic loci for age at menarche
    (Nature Publishing Group, 2014-10-02) Perry, John RB; Day, Felix; Elks, Cathy E.; Sulem, Patrick; Thompson, Deborah J.; Ferreira, Teresa; He, Chunyan; Chasman, Daniel I.; Esko, Tõnu; Thorleifsson, Gudmar; Albrecht, Eva; Ang, Wei Q.; Corre, Tanguy; Cousminer, Diana L.; Feenstra, Bjarke; Franceschini, Nora; Ganna, Andrea; Johnson, Andrew D.; Kjellqvist, Sanela; Lunetta, Kathryn L.; McMahon, George; Nolte, Ilja M.; Paternoster, Lavinia; Porcu, Eleonora; Smith, Albert V.; Stolk, Lisette; Teumer, Alexander; Tšernikova, Natalia; Tikkanen, Emmi; Ulivi, Sheila; Wagner, Erin K.; Amin, Najaf; Bierut, Laura J.; Byrne, Enda M.; Hottenga, Jouke-Jan; Koller, Daniel L.; Mangino, Massimo; Pers, Tune H.; Yerges-Armstrong, Laura M.; Zhao, Jing Hua; Andrulis, Irene L.; Anton-Culver, Hoda; Atsma, Femke; Bandinelli, Stefania; Beckmann, Matthias W.; Benitez, Javier; Blomqvist, Carl; Bojesen, Stig E.; Bolla, Manjeet K.; Bonanni, Bernardo; Brauch, Hiltrud; Brenner, Hermann; Buring, Julie E.; Chang-Claude, Jenny; Chanock, Stephen; Chen, Jinhui; Chenevix-Trench, Georgia; Collée, J. Margriet; Couch, Fergus J.; Couper, David; Coveillo, Andrea D.; Cox, Angela; Czene, Kamila; D’adamo, Adamo Pio; Smith, George Davey; De Vivo, Immaculata; Demerath, Ellen W.; Dennis, Joe; Devilee, Peter; Dieffenbach, Aida K.; Dunning, Alison M.; Eiriksdottir, Gudny; Eriksson, Johan G.; Fasching, Peter A.; Ferrucci, Luigi; Flesch-Janys, Dieter; Flyger, Henrik; Foroud, Tatiana; Franke, Lude; Garcia, Melissa E.; García-Closas, Montserrat; Geller, Frank; de Geus, Eco EJ; Giles, Graham G.; Gudbjartsson, Daniel F.; Gudnason, Vilmundur; Guénel, Pascal; Guo, Suiqun; Hall, Per; Hamann, Ute; Haring, Robin; Hartman, Catharina A.; Heath, Andrew C.; Hofman, Albert; Hooning, Maartje J.; Hopper, John L.; Hu, Frank B.; Hunter, David J.; Karasik, David; Kiel, Douglas P.; Knight, Julia A.; Kosma, Veli-Matti; Kutalik, Zoltan; Lai, Sandra; Lambrechts, Diether; Lindblom, Annika; Mägi, Reedik; Magnusson, Patrik K.; Mannermaa, Arto; Martin, Nicholas G.; Masson, Gisli; McArdle, Patrick F.; McArdle, Wendy L.; Melbye, Mads; Michailidou, Kyriaki; Mihailov, Evelin; Milani, Lili; Milne, Roger L.; Nevanlinna, Heli; Neven, Patrick; Nohr, Ellen A.; Oldehinkel, Albertine J.; Oostra, Ben A.; Palotie, Aarno; Peacock, Munro; Pedersen, Nancy L.; Peterlongo, Paolo; Peto, Julian; Pharoah, Paul DP; Postma, Dirkje S.; Pouta, Anneli; Pylkäs, Katri; Radice, Paolo; Ring, Susan; Rivadeneira, Fernando; Robino, Antonietta; Rose, Lynda M.; Rudolph, Anja; Salomaa, Veikko; Sanna, Serena; Schlessinger, David; Schmidt, Marjanka K.; Southey, Mellissa C.; Sovio, Ulla; Stampfer, Meir J.; Stöckl, Doris; Storniolo, Anna M.; Timpson, Nicholas J.; Tyrer, Jonathan; Visser, Jenny A.; Vollenweider, Peter; Völzke, Henry; Waeber, Gerard; Waldenberger, Melanie; Wallaschofski, Henri; Wang, Qin; Willemsen, Gonneke; Winqvist, Robert; Wolffenbuttel, Bruce HR; Wright, Margaret J.; Boomsma, Dorret I.; Econs, Michael J.; Khaw, Kay-Tee; Loos, Ruth JF; McCarthy, Mark I.; Montgomery, Grant W.; Rice, John P.; Streeten, Elizabeth A.; Thorsteinsdottir, Unnur; van Duijn, Cornelia M.; Alizadeh, Behrooz Z.; Bergmann, Sven; Boerwinkle, Eric; Boyd, Heather A.; Crisponi, Laura; Gasparini, Paolo; Gieger, Christian; Harris, Tamara B.; Ingelsson, Erik; Järvelin, Marjo-Riitta; Kraft, Peter; Lawlor, Debbie; Metspalu, Andres; Pennell, Craig E.; Ridker, Paul M.; Snieder, Harold; Sørensen, Thorkild IA; Spector, Tim D.; Strachan, David P.; Uitterlinden, André G.; Wareham, Nicholas J.; Widen, Elisabeth; Zygmunt, Marek; Murray, Anna; Easton, Douglas F.; Stefansson, Kari; Murabito, Joanne M.; Ong, Ken K.; Department of Epidemiology, Richard M. Fairbanks School of Public Health
    Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation,, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P<5×10−8) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1/WDR25, MKRN3/MAGEL2 and KCNK9) demonstrating parent-of-origin specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and gamma-aminobutyric acid-B2 receptor signaling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition.
  • Thumbnail Image
    Item
    Rare coding variants and X-linked loci associated with age at menarche
    (Nature Publishing Group, 2015-08-04) Lunetta, Kathryn L.; Day, Felix R.; Sulem, Patrick; Ruth, Katherine S.; Tung, Joyce Y.; Hinds, David A.; Esko, Tõnu; Elks, Cathy E.; Altmaier, Elisabeth; He, Chunyan; Huffman, Jennifer E.; Mihailov, Evelin; Porcu, Eleonora; Robino, Antonietta; Rose, Lynda M.; Schick, Ursula M.; Stolk, Lisette; Teumer, Alexander; Thompson, Deborah J.; Traglia, Michela; Wang, Carol A.; Yerges-Armstrong, Laura M.; Antoniou, Antonis C.; Barbieri, Caterina; Coviello, Andrea D.; Cucca, Francesco; Demerath, Ellen W.; Dunning, Alison M.; Gandin, Ilaria; Grove, Megan L.; Gudbjartsson, Daniel F.; Hocking, Lynne J.; Hofman, Albert; Huang, Jinyan; Jackson, Rebecca D.; Karasik, David; Kriebel, Jennifer; Lange, Ethan M.; Lange, Leslie A.; Langenberg, Claudia; Li, Xin; Luan, Jian'an; Mägi, Reedik; Morrison, Alanna C.; Padmanabhan, Sandosh; Pirie, Ailith; Polasek, Ozren; Porteous, David; Reiner, Alex P.; Rivadeneira, Fernando; Rudan, Igor; Sala, Cinzia F.; Schlessinger, David; Scott, Robert A.; Stöckl, Doris; Visser, Jenny A.; Völker, Uwe; Vozzi, Diego; Wilson, James G.; Zygmunt, Marek; Boerwinkle, Eric; Buring, Julie E.; Crisponi, Laura; Easton, Douglas F.; Hayward, Caroline; Hu, Frank B.; Liu, Simin; Metspalu, Andres; Pennell, Craig E.; Ridker, Paul M.; Strauch, Konstantin; Streeten, Elizabeth A.; Toniolo, Daniela; Uitterlinden, André G.; Ulivi, Sheila; Völzke, Henry; Wareham, Nicholas J.; Wellons, Melissa; Franceschini, Nora; Chasman, Daniel I.; Thorsteinsdottir, Unnur; Murray, Anna; Stefansson, Kari; Murabito, Joanne M.; Ong, Ken K.; Perry, John R. B.; Department of Epidemiology, Richard M. Fairbanks School of Public Health
    More than 100 loci have been identified for age at menarche by genome-wide association studies; however, collectively these explain only ~3% of the trait variance. Here we test two overlooked sources of variation in 192,974 European ancestry women: low-frequency protein-coding variants and X-chromosome variants. Five missense/nonsense variants (in ALMS1/LAMB2/TNRC6A/TACR3/PRKAG1) are associated with age at menarche (minor allele frequencies 0.08–4.6%; effect sizes 0.08–1.25 years per allele; P<5 × 10−8). In addition, we identify common X-chromosome loci at IGSF1 (rs762080, P=9.4 × 10−13) and FAAH2 (rs5914101, P=4.9 × 10−10). Highlighted genes implicate cellular energy homeostasis, post-transcriptional gene silencing and fatty-acid amide signalling. A frequently reported mutation in TACR3 for idiopathic hypogonatrophic hypogonadism (p.W275X) is associated with 1.25-year-later menarche (P=2.8 × 10−11), illustrating the utility of population studies to estimate the penetrance of reportedly pathogenic mutations. Collectively, these novel variants explain ~0.5% variance, indicating that these overlooked sources of variation do not substantially explain the ‘missing heritability’ of this complex trait.