Novel genetic loci underlying human intracranial volume identified through genome-wide association

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

doi:10.1038/nn.4398

Novel genetic loci underlying human intracranial volume identified through genome-wide association

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

Research output: Contribution to journal › Article › peer-review

Abstract

Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρ_genetic = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (N_combined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.

Original language	English
Pages (from-to)	1569–1582
Number of pages	14
Journal	Nature Neuroscience
Volume	19
Issue number	12
Early online date	3 Oct 2016
DOIs	https://doi.org/10.1038/nn.4398
Publication status	Published - 31 Dec 2016

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Novel genetic loci underlying human intracranial volume identified through genome-wide association
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Cite this

Adams, H. H. H., Hibar, D. P., Chouraki, V., Stein, J. L., Nyquist, P. A., Rentería, M. E., Trompet, S., Arias-Vasquez, A., Seshadri, S., Desrivières, S., Beecham, A. H., Jahanshad, N., Wittfeld, K., Van der Lee, S. J., Abramovic, L., Alhusaini, S., Amin, N., Andersson, M., Arfanakis, K., ... Thompson, P. M. (2016). Novel genetic loci underlying human intracranial volume identified through genome-wide association. Nature Neuroscience, 19(12), 1569–1582. https://doi.org/10.1038/nn.4398

@article{cef4fd4e02ab4e128153a6de64660b4d,

title = "Novel genetic loci underlying human intracranial volume identified through genome-wide association",

abstract = "Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.",

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

year = "2016",

month = dec,

day = "31",

doi = "10.1038/nn.4398",

language = "English",

volume = "19",

pages = "1569–1582",

journal = "Nature Neuroscience",

issn = "1097-6256",

publisher = "Nature Publishing Group",

number = "12",

}

Adams, HHH, Hibar, DP, Chouraki, V, Stein, JL, Nyquist, PA, Rentería, ME, Trompet, S, Arias-Vasquez, A, Seshadri, S, Desrivières, S, Beecham, AH, Jahanshad, N, Wittfeld, K, Van der Lee, SJ, Abramovic, L, Alhusaini, S, Amin, N, Andersson, M, Arfanakis, K, Aribisala, BS, Armstrong, NJ, Athanasiu, L, Axelsson, T, Beiser, A, Bernard, M, Bis, JC, Blanken, LME, Blanton, SH, Bohlken, MM, Boks, MP, Bralten, J, Brickman, AM, Carmichael, O, Chakravarty, MM, Chauhan, G, Chen, Q, Ching, CRK, Cuellar-Partida, G, Braber, AD, Doan, NT, Ehrlich, S, Filippi, I, Ge, T, Giddaluru, S, Goldman, AL, Gottesman, RF, Greven, CU, Grimm, O, Griswold, ME, Guadalupe, T, Hass, J, Haukvik, UK, Hilal, S, Hofer, E, Hoehn, D, Holmes, AJ, Hoogman, M, Janowitz, D, Jia, T, Kasperaviciute, D, Kim, S, Klein, M, Kraemer, B, Lee, PH, Liao, J, Liewald, DCM, Lopez, LM, Luciano, M, Macare, C, Marquand, A, Matarin, M, Mather, KA, Mattheisen, M, Mazoyer, B, McKay, DR, McWhirter, R, Milaneschi, Y, Mirza-Schreiber, N, Muetzel, RL, Maniega, SM, Nho, K, Nugent, AC, Loohuis, LMO, Oosterlaan, J, Papmeyer, M, Pappa, I, Pirpamer, L, Pudas, S, Pütz, B, Rajan, KB, Ramasamy, A, Richards, JS, Risacher, SL, Roiz-Santiañez, R, Rommelse, N, Rose, EJ, Royle, NA, Rundek, T, Sämann, PG, Satizabal, CL, Schmaal, L, Schork, AJ, Shen, L, Shin, J, Shumskaya, E, Smith, AV, Sprooten, E, Strike, LT, Teumer, A, Thomson, R, Tordesillas-Gutierrez, D, Toro, R, Trabzuni, D, Vaidya, D, Van der Grond, J, Van der Meer, D, Van Donkelaar, MMJ, Van Eijk, KR, Van Erp, TGM, Van Rooij, D, Walton, E, Westlye, LT, Whelan, CD, Windham, BG, Winkler, AM, Woldehawariat, G, Wolf, C, Wolfers, T, Xu, B, Yanek, LR, Yang, J, Zijdenbos, A, Zwiers, MP, Agartz, I, Aggarwal, NT, Almasy, L, Ames, D, Amouyel, P, Andreassen, OA, Arepalli, S, Assareh, AA, Barral, S, Bastin, ME, Becker, DM, Becker, JT, Bennett, DA, Blangero, J, van Bokhoven, H, Boomsma, DI, Brodaty, H, Brouwer, RM, Brunner, HG, Buckner, RL, Buitelaar, JK, Bulayeva, KB, Cahn, W, Calhoun, VD, Cannon, DM, Cavalleri, GL, Chen, C, Cheng, C-Y, Cichon, S, Cookson, MR, Corvin, A, Crespo-Facorro, B, Curran, JE, Czisch, M, Dale, AM, Davies, GE, De Geus, EJC, De Jager, PL, de Zubicaray, GI, Delanty, N, Depondt, C, DeStefano, AL, Dillman, A, Djurovic, S, Donohoe, G, Drevets, WC, Duggirala, R, Dyer, TD, Erk, S, Espeseth, T, Evans, DA, Fedko, IO, Fernández, G, Ferrucci, L, Fisher, SE, Fleischman, DA, Ford, I, Foroud, TM, Fox, PT, Francks, C, Fukunaga, M, Gibbs, JR, Glahn, DC, Gollub, RL, Göring, HHH, Grabe, HJ, Green, RC, Gruber, O, Gudnason, V, Guelfi, S, Hansell, NK, Hardy, J, Hartman, CA, Hashimoto, R, Hegenscheid, K, Heinz, A, Le Hellard, S, Hernandez, DG, Heslenfeld, DJ, Ho, B-C, Hoekstra, PJ, Hoffmann, W, Hofman, A, Holsboer, F, Homuth, G, Hosten, N, Hottenga, J-J, Pol, HEH, Ikeda, M, Ikram, MK, Jr, CRJ, Jenkinson, M, Johnson, R, Jönsson, EG, Jukema, JW, Kahn, RS, Kanai, R, Kloszewska, I, Knopman, DS, Kochunov, P, Kwok, JB, Lawrie, SM, Lemaître, H, Liu, X, Longo, DL, Jr, WTL, Lopez, OL, Lovestone, S, Martinez, O, Martinot, J-L, Mattay, VS, McDonald, C, McIntosh, AM, McMahon, KL, McMahon, FJ, Mecocci, P, Melle, I, Meyer-Lindenberg, A, Mohnke, S, Montgomery, GW, Morris, DW, Mosley, TH, Mühleisen, TW, Müller-Myhsok, B, Nalls, MA, Nauck, M, Nichols, TE, Niessen, WJ, Nöthen, MM, Nyberg, L, Ohi, K, Olvera, RL, Ophoff, RA, Pandolfo, M, Paus, T, Pausova, Z, Penninx, BWJH, Pike, GB, Potkin, SG, Psaty, BM, Reppermund, S, Rietschel, M, Roffman, JL, Romanczuk-Seiferth, N, Rotter, JI, Ryten, M, Sacco, RL, Sachdev, PS, Saykin, AJ, Schmidt, R, Schofield, PR, Sigurdsson, S, Simmons, A, Singleton, A, Sisodiya, SM, Smith, C, Smoller, JW, Soininen, H, Srikanth, V, Steen, VM, Stott, DJ, Sussmann, JE, Thalamuthu, A, Tiemeier, H, Toga, AW, Traynor, BJ, Troncoso, J, Turner, JA, Tzourio, C, Uitterlinden, AG, Hernández, MCV, Van der Brug, M, Van der Lugt, A, Van der Wee, NJA, Van Duijn, CM, Van Haren, NEM, Van 't Ent, D, Van Tol, M-J, Vardarajan, BN, Veltman, DJ, Vernooij, MW, Völzke, H, Walter, H, Wardlaw, JM, Wassink, TH, Weale, ME, Weinberger, DR, Weiner, MW, Wen, W, Westman, E, White, T, Wong, TY, Wright, CB, Zielke, HR, Zonderman, AB, Deary, IJ, DeCarli, C, Schmidt, H, Martin, NG, De Craen, AJM, Wright, MJ, Launer, LJ, Schumann, G, Fornage, M, Franke, B, Debette, S, Medland, SE, Ikram, MA & Thompson, PM 2016, 'Novel genetic loci underlying human intracranial volume identified through genome-wide association', Nature Neuroscience, vol. 19, no. 12, pp. 1569–1582. https://doi.org/10.1038/nn.4398

TY - JOUR

T1 - Novel genetic loci underlying human intracranial volume identified through genome-wide association

AU - Adams, Hieab H H

AU - Hibar, Derrek P

AU - Chouraki, Vincent

AU - Stein, Jason L

AU - Nyquist, Paul A

AU - Rentería, Miguel E

AU - Trompet, Stella

AU - Arias-Vasquez, Alejandro

AU - Seshadri, Sudha

AU - Desrivières, Sylvane

AU - Beecham, Ashley H

AU - Jahanshad, Neda

AU - Wittfeld, Katharina

AU - Van der Lee, Sven J

AU - Abramovic, Lucija

AU - Alhusaini, Saud

AU - Amin, Najaf

AU - Andersson, Micael

AU - Arfanakis, Konstantinos

AU - Aribisala, Benjamin S

AU - Armstrong, Nicola J

AU - Athanasiu, Lavinia

AU - Axelsson, Tomas

AU - Beiser, Alexa

AU - Bernard, Manon

AU - Bis, Joshua C

AU - Blanken, Laura M E

AU - Blanton, Susan H

AU - Bohlken, Marc M

AU - Boks, Marco P

AU - Bralten, Janita

AU - Brickman, Adam M

AU - Carmichael, Owen

AU - Chakravarty, M Mallar

AU - Chauhan, Ganesh

AU - Chen, Qiang

AU - Ching, Christopher R K

AU - Cuellar-Partida, Gabriel

AU - Braber, Anouk Den

AU - Doan, Nhat Trung

AU - Ehrlich, Stefan

AU - Filippi, Irina

AU - Ge, Tian

AU - Giddaluru, Sudheer

AU - Goldman, Aaron L

AU - Gottesman, Rebecca F

AU - Greven, Corina U

AU - Grimm, Oliver

AU - Griswold, Michael E

AU - Guadalupe, Tulio

AU - Hass, Johanna

AU - Haukvik, Unn K

AU - Hilal, Saima

AU - Hofer, Edith

AU - Hoehn, David

AU - Holmes, Avram J

AU - Hoogman, Martine

AU - Janowitz, Deborah

AU - Jia, Tianye

AU - Kasperaviciute, Dalia

AU - Kim, Sungeun

AU - Klein, Marieke

AU - Kraemer, Bernd

AU - Lee, Phil H

AU - Liao, Jiemin

AU - Liewald, David C M

AU - Lopez, Lorna M

AU - Luciano, Michelle

AU - Macare, Christine

AU - Marquand, Andre

AU - Matarin, Mar

AU - Mather, Karen A

AU - Mattheisen, Manuel

AU - Mazoyer, Bernard

AU - McKay, David R

AU - McWhirter, Rebekah

AU - Milaneschi, Yuri

AU - Mirza-Schreiber, Nazanin

AU - Muetzel, Ryan L

AU - Maniega, Susana Muñoz

AU - Nho, Kwangsik

AU - Nugent, Allison C

AU - Loohuis, Loes M Olde

AU - Oosterlaan, Jaap

AU - Papmeyer, Martina

AU - Pappa, Irene

AU - Pirpamer, Lukas

AU - Pudas, Sara

AU - Pütz, Benno

AU - Rajan, Kumar B

AU - Ramasamy, Adaikalavan

AU - Richards, Jennifer S

AU - Risacher, Shannon L

AU - Roiz-Santiañez, Roberto

AU - Rommelse, Nanda

AU - Rose, Emma J

AU - Royle, Natalie A

AU - Rundek, Tatjana

AU - Sämann, Philipp G

AU - Satizabal, Claudia L

AU - Schmaal, Lianne

AU - Schork, Andrew J

AU - Shen, Li

AU - Shin, Jean

AU - Shumskaya, Elena

AU - Smith, Albert V

AU - Sprooten, Emma

AU - Strike, Lachlan T

AU - Teumer, Alexander

AU - Thomson, Russell

AU - Tordesillas-Gutierrez, Diana

AU - Toro, Roberto

AU - Trabzuni, Daniah

AU - Vaidya, Dhananjay

AU - Van der Grond, Jeroen

AU - Van der Meer, Dennis

AU - Van Donkelaar, Marjolein M J

AU - Van Eijk, Kristel R

AU - Van Erp, Theo G M

AU - Van Rooij, Daan

AU - Walton, Esther

AU - Westlye, Lars T

AU - Whelan, Christopher D

AU - Windham, Beverly G

AU - Winkler, Anderson M

AU - Woldehawariat, Girma

AU - Wolf, Christiane

AU - Wolfers, Thomas

AU - Xu, Bing

AU - Yanek, Lisa R

AU - Yang, Jingyun

AU - Zijdenbos, Alex

AU - Zwiers, Marcel P

AU - Agartz, Ingrid

AU - Aggarwal, Neelum T

AU - Almasy, Laura

AU - Ames, David

AU - Amouyel, Philippe

AU - Andreassen, Ole A

AU - Arepalli, Sampath

AU - Assareh, Amelia A

AU - Barral, Sandra

AU - Bastin, Mark E

AU - Becker, Diane M

AU - Becker, James T

AU - Bennett, David A

AU - Blangero, John

AU - van Bokhoven, Hans

AU - Boomsma, Dorret I

AU - Brodaty, Henry

AU - Brouwer, Rachel M

AU - Brunner, Han G

AU - Buckner, Randy L

AU - Buitelaar, Jan K

AU - Bulayeva, Kazima B

AU - Cahn, Wiepke

AU - Calhoun, Vince D

AU - Cannon, Dara M

AU - Cavalleri, Gianpiero L

AU - Chen, Christopher

AU - Cheng, Ching-Yu

AU - Cichon, Sven

AU - Cookson, Mark R

AU - Corvin, Aiden

AU - Crespo-Facorro, Benedicto

AU - Curran, Joanne E

AU - Czisch, Michael

AU - Dale, Anders M

AU - Davies, Gareth E

AU - De Geus, Eco J C

AU - De Jager, Philip L

AU - de Zubicaray, Greig I

AU - Delanty, Norman

AU - Depondt, Chantal

AU - DeStefano, Anita L

AU - Dillman, Allissa

AU - Djurovic, Srdjan

AU - Donohoe, Gary

AU - Drevets, Wayne C

AU - Duggirala, Ravi

AU - Dyer, Thomas D

AU - Erk, Susanne

AU - Espeseth, Thomas

AU - Evans, Denis A

AU - Fedko, Iryna O

AU - Fernández, Guillén

AU - Ferrucci, Luigi

AU - Fisher, Simon E

AU - Fleischman, Debra A

AU - Ford, Ian

AU - Foroud, Tatiana M

AU - Fox, Peter T

AU - Francks, Clyde

AU - Fukunaga, Masaki

AU - Gibbs, J Raphael

AU - Glahn, David C

AU - Gollub, Randy L

AU - Göring, Harald H H

AU - Grabe, Hans J

AU - Green, Robert C

AU - Gruber, Oliver

AU - Gudnason, Vilmundur

AU - Guelfi, Sebastian

AU - Hansell, Narelle K

AU - Hardy, John

AU - Hartman, Catharina A

AU - Hashimoto, Ryota

AU - Hegenscheid, Katrin

AU - Heinz, Andreas

AU - Le Hellard, Stephanie

AU - Hernandez, Dena G

AU - Heslenfeld, Dirk J

AU - Ho, Beng-Choon

AU - Hoekstra, Pieter J

AU - Hoffmann, Wolfgang

AU - Hofman, Albert

AU - Holsboer, Florian

AU - Homuth, Georg

AU - Hosten, Norbert

AU - Hottenga, Jouke-Jan

AU - Pol, Hilleke E Hulshoff

AU - Ikeda, Masashi

AU - Ikram, M Kamran

AU - Jr, Clifford R Jack

AU - Jenkinson, Mark

AU - Johnson, Robert

AU - Jönsson, Erik G

AU - Jukema, J Wouter

AU - Kahn, René S

AU - Kanai, Ryota

AU - Kloszewska, Iwona

AU - Knopman, David S

AU - Kochunov, Peter

AU - Kwok, John B

AU - Lawrie, Stephen M

AU - Lemaître, Hervé

AU - Liu, Xinmin

AU - Longo, Dan L

AU - Jr, W T Longstreth

AU - Lopez, Oscar L

AU - Lovestone, Simon

AU - Martinez, Oliver

AU - Martinot, Jean-Luc

AU - Mattay, Venkata S

AU - McDonald, Colm

AU - McIntosh, Andrew M

AU - McMahon, Katie L

AU - McMahon, Francis J

AU - Mecocci, Patrizia

AU - Melle, Ingrid

AU - Meyer-Lindenberg, Andreas

AU - Mohnke, Sebastian

AU - Montgomery, Grant W

AU - Morris, Derek W

AU - Mosley, Thomas H

AU - Mühleisen, Thomas W

AU - Müller-Myhsok, Bertram

AU - Nalls, Michael A

AU - Nauck, Matthias

AU - Nichols, Thomas E

AU - Niessen, Wiro J

AU - Nöthen, Markus M

AU - Nyberg, Lars

AU - Ohi, Kazutaka

AU - Olvera, Rene L

AU - Ophoff, Roel A

AU - Pandolfo, Massimo

AU - Paus, Tomas

AU - Pausova, Zdenka

AU - Penninx, Brenda W J H

AU - Pike, G Bruce

AU - Potkin, Steven G

AU - Psaty, Bruce M

AU - Reppermund, Simone

AU - Rietschel, Marcella

AU - Roffman, Joshua L

AU - Romanczuk-Seiferth, Nina

AU - Rotter, Jerome I

AU - Ryten, Mina

AU - Sacco, Ralph L

AU - Sachdev, Perminder S

AU - Saykin, Andrew J

AU - Schmidt, Reinhold

AU - Schofield, Peter R

AU - Sigurdsson, Sigurdur

AU - Simmons, Andy

AU - Singleton, Andrew

AU - Sisodiya, Sanjay M

AU - Smith, Colin

AU - Smoller, Jordan W

AU - Soininen, Hilkka

AU - Srikanth, Velandai

AU - Steen, Vidar M

AU - Stott, David J

AU - Sussmann, Jessika E

AU - Thalamuthu, Anbupalam

AU - Tiemeier, Henning

AU - Toga, Arthur W

AU - Traynor, Bryan J

AU - Troncoso, Juan

AU - Turner, Jessica A

AU - Tzourio, Christophe

AU - Uitterlinden, Andre G

AU - Hernández, Maria C Valdés

AU - Van der Brug, Marcel

AU - Van der Lugt, Aad

AU - Van der Wee, Nic J A

AU - Van Duijn, Cornelia M

AU - Van Haren, Neeltje E M

AU - Van 't Ent, Dennis

AU - Van Tol, Marie-Jose

AU - Vardarajan, Badri N

AU - Veltman, Dick J

AU - Vernooij, Meike W

AU - Völzke, Henry

AU - Walter, Henrik

AU - Wardlaw, Joanna M

AU - Wassink, Thomas H

AU - Weale, Michael E

AU - Weinberger, Daniel R

AU - Weiner, Michael W

AU - Wen, Wei

AU - Westman, Eric

AU - White, Tonya

AU - Wong, Tien Y

AU - Wright, Clinton B

AU - Zielke, H Ronald

AU - Zonderman, Alan B

AU - Deary, Ian J

AU - DeCarli, Charles

AU - Schmidt, Helena

AU - Martin, Nicholas G

AU - De Craen, Anton J M

AU - Wright, Margaret J

AU - Launer, Lenore J

AU - Schumann, Gunter

AU - Fornage, Myriam

AU - Franke, Barbara

AU - Debette, Stéphanie

AU - Medland, Sarah E

AU - Ikram, M Arfan

AU - Thompson, Paul M

PY - 2016/12/31

Y1 - 2016/12/31

N2 - Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.

AB - Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.

U2 - 10.1038/nn.4398

DO - 10.1038/nn.4398

M3 - Article

C2 - 27694991

SN - 1097-6256

VL - 19

SP - 1569

EP - 1582

JO - Nature Neuroscience

JF - Nature Neuroscience

IS - 12

ER -

Novel genetic loci underlying human intracranial volume identified through genome-wide association

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Novel genetic loci underlying human intracranial volume identified through genome-wide association

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