Novel genetic loci underlying human intracranial volume identified through genome-wide association
Year: 2020
Type: article
Study design: Observational Study
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 novel loci for intracranial volume and confirmed two known signals. Four of the loci are 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 indicated a similar genetic background and allowed for the identification of four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, Parkinson’s disease, and enriched near genes involved in growth pathways including PI3K–AKT signaling. These findings identify biological underpinnings of intracranial volume and provide genetic support for theories on brain reserve and brain overgrowth.
Source: UNC Libraries
DOI: 10.17615/3f6m-6s62
Authors: Walter, Henrik, McMahon, Katie L, Marquand, Andre, Yang, Jingyun, Aggarwal, Neelum T, Thalamuthu, Anbupalam, Cavalleri, Gianpiero L, Hoffmann, Wolfgang, Hardy, John, Brunner, Han G, Pike, G Bruce, Drevets, Wayne C, Gibbs, J Raphael, White, Tonya, Sussmann, Jessika E, Van Erp, Theo G M, Kasperaviciute, Dalia, Van Der Lugt, Aad, Nugent, Allison C, Medland, Sarah E, Ophoff, Roel A, Fedko, Iryna O, Ehrlich, Stefan, Jack, Clifford R, Ferrucci, Luigi, Hilal, Saima, Cahn, Wiepke, Tordesillas-Gutierrez, Diana, Paus, Tomas, Le Hellard, Stephanie, Van Tol, Marie-Jose, Turner, Jessica A, Rietschel, Marcella, Gudnason, Vilmundur, Matarin, Mar, Tiemeier, Henning, Aribisala, Benjamin S, Pappa, Irene, Toro, Roberto, Longstreth,, Jenkinson, Mark, Rajan, Kumar B, Davies, Gareth E, Liu, Xinmin, Guelfi, Sebastian, Nichols, Thomas E, Buitelaar, Jan K, Montgomery, Grant W, Göring, Harald H H, Smoller, Jordan W, McDonald, Colm, Pütz, Benno, Duggirala, Ravi, Jahanshad, Neda, Sisodiya, Sanjay M, Holsboer, Florian, Yanek, Lisa R, Sprooten, Emma, Roiz-Santiañez, Roberto, Franke, Barbara, Chauhan, Ganesh, Fornage, Myriam, Jukema, J Wouter, Royle, Natalie A, Cichon, Sven, Schumann, Gunter, Gruber, Oliver, Völzke, Henry, Rommelse, Nanda, Blanken, Laura M E, Wassink, Thomas H, Van Duijn, Cornelia M, Giddaluru, Sudheer, Delanty, Norman, Corvin, Aiden, Nöthen, Markus M, Bastin, Mark E, Doan, Nhat Trung, Agartz, Ingrid, Olvera, Rene L, Alhusaini, Saud, Hottenga, Jouke-Jan, Bernard, Manon, Zonderman, Alan B, Lopez, Lorna M, Becker, James T, Czisch, Michael, Lopez, Oscar L, Schmidt, Helena, Trabzuni, Daniah, Djurovic, Srdjan, Westlye, Lars T, Guadalupe, Tulio, Axelsson, Tomas, Simmons, Andy, Jia, Tianye, Amin, Najaf, Arias-Vasquez, Alejandro, Milaneschi, Yuri, Erk, Susanne, Armstrong, Nicola J, Ge, Tian, Lemaître, Hervé, Destefano, Anita L, Ching, Christopher R K, Ohi, Kazutaka, Richards, Jennifer S, Shumskaya, Elena, Andersson, Micael, Vaidya, Dhananjay, Seshadri, Sudha, Ryten, Mina, McKay, David R, Trompet, Stella, Mattay, Venkata S, Van't Ent, Dennis, Hibar, Derrek P, Wolf, Christiane, Roffman, Joshua L, Risacher, Shannon L, Goldman, Aaron L, Van Der Brug, Marcel, Pandolfo, Massimo, Hosten, Norbert, Pirpamer, Lukas, Kwok, John B, Boomsma, Dorret I, Xu, Bing, Wright, Margaret J, Zijdenbos, Alex, Weiner, Michael W, Windham, Beverly G, Van Der Grond, Jeroen, Singleton, Andrew, Wright, Clinton B, Steen, Vidar M, Mosley, Thomas H, Van Der Lee, Sven J, De Jager, Philip L, Wardlaw, Joanna M, Muetzel, Ryan L, Brickman, Adam M, Rotter, Jerome I, Van Donkelaar, Marjolein M J, Jönsson, Erik G, Martin, Nicholas G, Teumer, Alexander, Cannon, Dara M, Meyer-Lindenberg, Andreas, Hansell, Narelle K, Lovestone, Simon, Martinot, Jean-Luc, Fleischman, Debra A, Smith, Albert V, Kanai, Ryota, Vernooij, Meike W, Arepalli, Sampath, Psaty, Bruce M, Lawrie, Stephen M, Strike, Lachlan T, Bohlken, Marc M, Blangero, John, Zielke, H Ronald, Melle, Ingrid, Heinz, Andreas, Bralten, Janita, Barral, Sandra, Hoekstra, Pieter J, Cuellar-Partida, Gabriel, Mattheisen, Manuel, Curran, Joanne E, Hofman, Albert, Nyquist, Paul A, Mirza-Schreiber, Nazanin, Schmaal, Lianne, Nho, Kwangsik, Van Eijk, Kristel R, Pudas, Sara, Desrivières, Sylvane, Bulayeva, Kazima B, Soininen, Hilkka, Zwiers, Marcel P, Bennett, David A, Potkin, Steven G, Launer, Lenore J, Kim, Sungeun, Deary, Ian J, Shin, Jean, Hashimoto, Ryota, Brouwer, Rachel M, Papmeyer, Martina, Chen, Christopher, Braber, Anouk Den, Filippi, Irina, Liewald, David C M, Fisher, Simon E, Vardarajan, Badri N, Martinez, Oliver, Sämann, Philipp G, Mohnke, Sebastian, Kraemer, Bernd, Janowitz, Deborah, Gottesman, Rebecca F, Smith, Colin, Van Der Wee, Nic J A, Kloszewska, Iwona, Bis, Joshua C, Reppermund, Simone, Hernandez, Dena G, Veltman, Dick J, Weinberger, Daniel R, Sacco, Ralph L, Beiser, Alexa, Espeseth, Thomas, Beecham, Ashley H, Saykin, Andrew J, Penninx, Brenda W J H, Ikram, M Kamran, Arfanakis, Konstantinos, Buckner, Randy L, Assareh, Amelia A, Rundek, Tatjana, Stott, David J, Wen, Wei, Van Bokhoven, Hans, Nauck, Matthias, Niessen, Wiro J, Hoehn, David, Abramovic, Lucija, Cookson, Mark R, Hartman, Catharina A, Uitterlinden, Andre G, Weale, Michael E, Müller-Myhsok, Bertram, Srikanth, Velandai, Morris, Derek W, Maniega, Susana Muñoz, Wong, Tien Y, Kochunov, Peter, Foroud, Tatiana M, Holmes, Avram J, Dillman, Allissa, Hofer, Edith, Kahn, René S, Woldehawariat, Girma, Mazoyer, Bernard, De Geus, Eco J C, Grimm, Oliver, Mühleisen, Thomas W, Troncoso, Juan, Macare, Christine, McWhirter, Rebekah, Francks, Clyde, Hegenscheid, Katrin, Schmidt, Reinhold, Luciano, Michelle, Thomson, Russell, Chakravarty, M Mallar, Pol, Hilleke E Hulshoff, Thompson, Paul M., Greven, Corina U, Depondt, Chantal, Chen, Qiang, Homuth, Georg, Cheng, Ching-Yu, Van Der Meer, Dennis, Chouraki, Vincent, Ramasamy, Adaikalavan, Debette, Stéphanie, McMahon, Francis J, Fukunaga, Masaki, Evans, Denis A, Amouyel, Philippe, Traynor, Bryan J, Rentería, Miguel E, Blanton, Susan H, Tzourio, Christophe, Griswold, Michael E, Schofield, Peter R, Crespo-Facorro, Benedicto, Liao, Jiemin, Sachdev, Perminder S, Satizabal, Claudia L, Longo, Dan L, Winkler, Anderson M, Dale, Anders M, Sigurdsson, Sigurdur, Klein, Marieke, Haukvik, Unn K, Dyer, Thomas D, Glahn, David C, Walton, Esther, Ikram, M Arfan, Almasy, Laura, Athanasiu, Lavinia, Carmichael, Owen, Mather, Karen A, Rose, Emma J, Stein, Jason L, Donohoe, Gary, Oosterlaan, Jaap, Van Haren, Neeltje E M, Fox, Peter T, Ho, Beng-Choon, Andreassen, Ole A, Johnson, Robert, Whelan, Christopher D, Ford, Ian, Heslenfeld, Dirk J, Boks, Marco P, Loohuis, Loes M Olde, Westman, Eric, Brodaty, Henry, Knopman, David S, Romanczuk-Seiferth, Nina, Gollub, Randy L, Shen, Li, Mecocci, Patrizia, De Zubicaray, Greig I, Becker, Diane M, Wittfeld, Katharina, Hass, Johanna, De Craen, Anton J M, Grabe, Hans J, Hoogman, Martine, McIntosh, Andrew M, Green, Robert C, Schork, Andrew J, Nalls, Michael A, Wolfers, Thomas, Decarli, Charles, Ikeda, Masashi, Ames, David, Calhoun, Vince D, Fernández, Guillén, Nyberg, Lars, Van Rooij, Daan, Toga, Arthur W, Pausova, Zdenka, Hernández, Maria C Valdés, Adams, Hieab H H, Lee, Phil H
Institution: University of North Carolina at Chapel Hill
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Funder: Medical Research Council
Award: G5067462658
OpenAlex ID: W4300613495