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

Hieab H H Adams 1 Derrek P Hibar 2 Vincent Chouraki 3, 4 Jason L Stein 2 Paul A Nyquist 5 Miguel E Rentería 6 Stella Trompet 7 Alejandro Arias-Vasquez 8 Sudha Seshadri 3 Sylvane Desrivières 9 Ashley H Beecham 10 Neda Jahanshad 11 Katharina Wittfeld 12, 13 Sven J. van der Lee 1 Lucija Abramovic Saud Alhusaini 14, 15 Najaf Amin Micael Andersson 16 Konstantinos Arfanakis 17, 18 Benjamin S Aribisala 19, 20 Nicola J Armstrong 21, 22 Lavinia Athanasiu 23 Tomas Axelsson 24 Alex Beiser 3, 25 Bernard Bernard 26 Joshua C Bis 27 Laura Blanken 1 Susan H Blanton 10 Mar Bohlken Mar Boks Janita Bralten 28 Adam M Brickman 29 Owen Carmichael 30 M Mallar Chakravarty 31, 32 Ganesh Chauhan 33 Qiang Chen 34 Christophe Ching 2, 35 Gabriel Cuellar-Partida 6 Anouk Den Braber 36 Nhat Trung Doan 23 Stefan Ehrlich 37, 38 Irina Filippi 39, 40 Tian Ge 38, 41 Sudheer Giddaluru 42, 43 Aaron L Goldman 34 Rebecca F Gottesman 44 Corina U Greven 8, 9 Oliver Grimm 45 Michael E Griswold 46 Tulio Guadalupe 47, 48 Johanna Hass 37 Unn K Haukvik Saima Hilal 49 Edith Hofer 50 David Hoehn 51 Avram J. Holmes 38, 52 Martine Hoogman 8 Deborah Janowitz 13 Tianye Jia 9 Dalia Kasperaviciute 53, 54 Sungeun Kim 55 Marieke Klein Bernd Kraemer 56 Phil H Lee 41 Li Liao David C Liewald 19 Lorna M Lopez Michelle Luciano 57 Christine Macare 9 Mar Marquand Mar Matarin 58 Karen A Mather 59 Manuel Mattheisen 60, 61, 62 Bernard Mazoyer 63 David Mckay 64 Rebekah Mcwhirter Yuri Milaneschi 65 Nazanin Mirza-Schreiber Ryan L Muetzel 66 Susana Muñoz Maniega Kwangsik Nho 67, 68 Allison C Nugent 69 Loes M Olde Loohuis Jaap Oosterlaan Martina Martin Irene Pappa Lukas Pirpamer Sara Pudas Benno Pütz 70 Kumar B Rajan 18 Adaikalavan Ramasamy 71 Jennifer S Richards Shannon L Risacher 67, 68 Robert Roiz-Santiañez 72 Nanda Rommelse 28, 73 Emma Rose 74 Natalie A Royle 19 Tatjana Rundek Philipp G Sämann 51 Claudia L Satizabal 75 Li Schmaal 65 Andrew Schork 76, 77 Li Shen 68 Jean Shin Elena Shumskaya Albert Smith Emma Sprooten 64 Lachlan T Strike 78, 79, 80 Alex Teumer 81 Russell Thomson Diana Tordesillas-Gutierrez Roberto Toro 82 Daniah Trabzuni 83, 84 Dhananjay Vaidya Jeroen van der Grond 85 Dennis van der Meer 86 Marjolein M J van Donkelaar 28 Kristel R van Eijk Theo G M van Erp 87 Daan van Rooij 88 Esther Walton 89 Lars Westlye 90 Christophe Whelan Beverly G Windham 23 Anderson M Winkler 91 Girma Woldehawariat 92 Christiane Wolf Thomas W Wolfers Bing Xu Lisa R Yanek 93 Jingyun Yang Alex Zijdenbos 94 Marcel Zwiers 28 Ingrid Agartz 95 Neelum T Aggarwal Laura Almasy 96 David A Ames 97 Philippe Amouyel 4 Andreas Andreassen Sampath Arepalli 98 Amelia A Assareh 99 Sandra Barral 100 Mark Bastin 19 Diane M Becker James T Becker 101 David A Bennett John B Blangero 102, 103 Hans van Bokhoven 104 Dorret I Boomsma 81 Henry Brodaty 105, 106 Rachel M Brouwer 107 Han G Brunner 108 Randy L Buckner 109 Jan K Buitelaar 88 Kazima B Bulayeva 110 Wiepke Cahn 111 Vince D Calhoun 112, 113 Dara M Cannon 114 Gianpiero L Cavalleri 115 Christophe Chen 116 Ching-Yu Cheng Sven Cichon 117, 118, 61, 62 Mark Cookson 119 Aiden Corvin 120, 121 Benedicto Crespo-Facorro 72 Joanne E Curran 122 Michael Czisch 123 Anders M Dale 124 Gareth E Davies 125 Eco J C de Geus 57 Philip L de Jager 126, 127, 128 Greig I de Zubicaray 129 Norman Delanty 130, 131 Chantal Depondt 132 Anita L Destefano 133 Allissa Dillman 134 Srdjan Djurovic Gary Donohoe 114, 121 Wayne C Drevets 114 Ravi Duggirala 103 Thomas Dyer 102, 103 Susanne Erk 135 Thomas E Espeseth 90 Denis A Evans Iryna O Fedko 136 Guillén Fernández Luigi Ferrucci Simon Fisher 88 Debra A Fleischman 137 Ian Ford Tatiana M Foroud 138 Peter Fox 102, 139 Clyde Francks 48, 28 Masaki Fukunaga 140 J Raphael Gibbs 141 David C Glahn 64 Randy L Gollub 142 Harald H H Göring 143 Hans J Grabe 144 Robert Green 145 Oliver Gruber Vilmundur Gudnason 146, 147 Sebastian Guelfi 84 Narelle K Hansell 57 John Hardy 148 Catharina A Hartman 57 Ryota Hashimoto 149 Katrin Hegenscheid 13 Andreas Heinz Stephanie Le Hellard Dena G Hernandez Dirk J Heslenfeld 13 Beng-Choon Ho 150 Pieter J Hoekstra 151 Wolfgang Hoffmann Albert Hofman Florian Holsboer 152 Georg Homuth 153 Norbert Hosten 13 Jouke-Jan Hottenga 81 Hilleke E Hulshoff Pol Masashi Ikeda 154 M Kamran Ikram 155 Clifford R Jack Jr Mark Jenkinson Robert Johnson 156 Erik G Jönsson 157, 158 J Wouter Jukema 159 René S Kahn Ryota Kanai 160, 161 Iwona Kloszewska 162 David S Knopman 163 Peter Kochunov 164 John B Kwok 165 Stephen M Lawrie 19 Hervé Lemaître 166 Xinmin Liu Dan L Longo 167 W T Longstreth Jr Oscar L Lopez 168 Simon Lovestone 169 Oliver Martin Jean-Luc Martin Venkata S Mattay 170 Colm Mcdonald 171 Andrew Mcintosh 172 Katie L Mcmahon 173 Francis J Mcmahon Patrizia Mecocci 174 Ingrid Melle 175, 176, 177, 95 Andreas Meyer-Lindenberg 178 Sebastian Mohnke 179 Grant W Montgomery 80, 180 Derek W Morris 181 Thomas H Mosley Thomas W Mühleisen 61, 62 Bertram Müller-Myhsok 182 Michael A Nalls 183 Matthias Nauck 184 Thomas E Nichols 185, 186 Wiro J Niessen 187 Markus M Nöthen 188 Lars Nyberg 189 Kazutaka Ohi 190 Rene L Olvera 191 Roel A Ophoff 192 Massimo Pandolfo 132 Tomas Paus 193 Zdenka Pausova 194 Brenda W J H Penninx 180 G Bruce Pike Steven G Potkin 195 Bruce M Psaty 196 Simone Reppermund 106 Marcel Rietschel 197, 198 Joshua L Roffman 199 Nina Romanczuk-Seiferth 179 Jerome I Rotter 200 Mina Ryten 201, 84 Ralph L Sacco 116 Perminder S Sachdev 202 Andrew Saykin 179, 67, 68 Reinhold Schmidt Peter R Schofield 203 Sigurdur Sigurdsson 204, 205 Andy Simmons Andrew Singleton 183 Sanjay M Sisodiya 206 Colin Smith Jordan W Smoller 38 Hilkka Soininen 207 Velandai Srikanth 208, 209 Vidar M Steen David J Stott 210 Jessika E Sussmann 19 Anbupalam Thalamuthu 211 Henning Tiemeier 212 Arthur W Toga 213 Bryan J Traynor 214 Juan Troncoso Jessica A Turner 215 Christophe Tzourio 216 Andre G Uitterlinden Maria C Valdés Hernández Marcel van der Brug 217 Aad van der Lugt 218 Nic J A van der Wee 219 Cornelia M van Duijn Neeltje E M van Haren Dennis van ′t Ent Marie-Jose van Tol 7 Badri N Vardarajan Dick J Veltman 65 Meike W Vernooij 220, 218 Henry Völzke 221 Henrik Walter 179, 222 Joanna M Wardlaw 19 Thomas H Wassink 223 Michael E Weale 224 Wei Weinberger Wei Weiner Wei Wen 225 Eric Westman 226 Tonya White 227 Tien Y Wong 228 Clinton B Wright 229 H Ronald Zielke Alan B Zonderman 92 Ian J Deary 19 Charles Decarli 230 Helena Schmidt 231 Nicholas G Martin Anton J M de Craen 232 Margaret J Wright 233 Lenore J Launer Gunter Schumann 234 Myriam Fornage 102, 235 Barbara Franke 88 Stéphanie Debette 216 Sarah E Medland 80 M Arfan Ikram * Paul M Thompson 11, *
* Corresponding author
63 GIN - Groupe d'imagerie neurofonctionnelle
IMN - Institut des Maladies Neurodégénératives [Bordeaux], CEA - Commissariat à l'énergie atomique et aux énergies alternatives
134 Laboratory of Neurogenetics
NIH - National Institutes of Health [Bethesda]
183 Laboratory of Neurogenetics
NIH - National Institutes of Health [Bethesda]
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.
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Journal articles
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https://hal.archives-ouvertes.fr/hal-01382716
Contributor : Gin Hal <>
Submitted on : Monday, October 17, 2016 - 2:28:37 PM
Last modification on : Friday, July 10, 2020 - 7:58:59 AM

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Hieab H H Adams, Derrek P Hibar, Vincent Chouraki, Jason L Stein, Paul A Nyquist, et al.. Novel genetic loci underlying human intracranial volume identified through genome-wide association. Nature Neuroscience, Nature Publishing Group, 2016, 19 (12), pp.1569-1582. ⟨10.1038/nn.4398⟩. ⟨hal-01382716⟩

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