Novel genetic loci associated with hippocampal volume

Derrek P. Hibar 1, 2 Hieab H. H. Adams 3, 2 Neda Jahanshad 1, 2 Ganesh Chauhan 4, 2 Jason L. Stein 5, 2 Edith Hofer 5, 2 Miguel E. Renteria 6, 2 Joshua C. Bis 7, 2 Alejandro Arias-Vasquez 8, 9, 2 M. Kamran Ikram 2 Sylvane Desrivières 10, 2 Meike W. Vernooij 2 Lucija Abramovic 11, 2 Saud Alhusaini 12, 13, 2 Najaf Amin 14, 2 Micael Andersson 15, 2 Konstantinos Arfanakis 16, 17, 2 Benjamin S. Aribisala 18, 19, 20, 2 Nicola J. Armstrong 21, 2 Lavinia Athanasiu 22, 23, 2 Tomas Axelsson 24, 2 Ashley H. Beecham 25, 2 Alex Beiser 26, 27, 2 Manon Bernard 28, 2 Susan H. Blanton 29, 2 Marc Bohlken 11, 2 Marco Boks 11, 2 Janita Bralten 30, 31, 32, 2 Adam M. Brickman 5, 2 Owen Carmichael 33, 2 M. Mallar Chakravarty 34, 2 Qiang Chen 5, 2 Christopher Ching 5, 2 Vincent Chouraki 35, 2 Gabriel Cuellar-Partida 6, 2 Fabrice Crivello 36, 2 Anouk Den Braber 5, 2 Nhat Trung Doan 37, 2 Stefan Ehrlich 38, 2 Sudheer Giddaluru 39, 40, 2 Aaron L. Goldman 41, 2 Rebecca F. Gottesman 42, 2 Oliver Grimm 5, 2 Michael E. Griswold 5, 2 Tulio Guadalupe 43, 44, 2 Boris A. Gutman 45, 46, 2 Johanna Hass 47, 2 Unn K. Haukvik 22, 2 David Hoehn 5, 2 Avram J. Ho 48, 2 Martine Hoogman 5, 2 Deborah Janowitz 49, 2 Tianye Jia 50, 2 Kjetil N. Jørgensen 51, 2 Nazanin Karbalai 5, 2 Dalia Kasperaviciute 52, 53, 2 Sungeun Kim 2 Marieke Klein 54, 2 Bernd Kraemer 55, 2 Phil H. Lee 5, 2 David C. Liewald 56, 2 Lorna M. Lopez 2 Michelle Luciano 57, 2 Christine Macare 10, 2 André F. Marquand 2 Mar Matarin 58, 2 Karen A. Mather 59, 2 Manuel Mattheisen 60, 61, 62, 2 David Mckay 2 Yuri Milaneschi 63, 2 Susana Muñoz Maniega 2 Kwangsik Nho 64, 65, 66, 2 Allison C. Nugent 67, 2 Paul Nyquist 68, 2 Loes M. Olde Loohuis 2 Jaap Oosterlaan 2 Martina Papmeyer 2 Lukas Pirpamer 2 Benno Pütz 69, 2 Adaikalavan Ramasamy 70, 2 Jennifer S. Richards 2 Shannon L. Risacher 64, 66, 2 Robert Roiz-Santiañez 71, 2 Nanda Rommelse 72, 73, 2 Stefan Ropele 74, 2 Emma Rose 75, 2 Natalie A. Royle 2 Tatjana Rundek 2 Philipp G. Sämann 76, 2 Arvin Saremi 2 Claudia L. Satizabal 77, 2 Lianne Schmaal 63, 2 Andrew Schork 78, 79, 2 Li Shen 80, 2 Jean Shin 2 Elena Shumskaya 5, 2 Albert Smith 81, 2 Emma Sprooten 82, 2 Lachlan T. Strike 83, 84, 85, 2 Alexander Teumer 2 Diana Tordesillas-Gutierrez 2 Robert Toro 86, 2 Daniah Trabzuni 87, 88, 2 Stella Trompet 2 Dhananjay Vaidya 2 Jeroen Van Der Grond 89, 2 Sven Van Der Lee 2 Dennis Van Der Meer 90, 2 Marjolein M. J. Van Donkelaar 30, 32, 2 Kristel R. Van Eijk 91, 2 Theo G. M. Van Erp 92, 2 Daan Van Rooij 93, 2 Esther Walton 94, 2 Lars Westlye 22, 95, 2 Christophe Whelan 1, 2 Beverly G. Windham 96, 2 Anderson M. Winkler 2 Katharina Wittfeld 49, 97, 2 Girma Woldehawariat 98, 2 Christiane Wolf 2 Thomas Wolfers 5, 2 Lisa R. Yanek 2 Jingyun Yang 2 Alex Zijdenbos 99, 2 Marcel Zwiers 32, 2 Ingrid Agartz 100, 2 Laura Almasy 101, 2 David Ames 102, 2 Philippe Amouyel 103, 2 Ole A Andreassen 2 Sampath Arepalli 104, 2 Amelia A. Assareh 2 Sandra Barral 2 Mark Bastin 105, 2 Diane M. Becker 2 James T. Becker 2 David A. Bennett 106, 2 John Blangero 107, 108, 2 Hans Van Bokhoven 109, 2 Dorret I. Boomsma 2 Henry Brodaty 110, 111, 2 Rachel M. Brouwer 112, 2 Han G. Brunner 2 Randy L. Buckner 113, 2 Jan K. Buitelaar 114, 2 Kazima B. Bulayeva 115, 2 Wiepke Cahn 116, 2 Vince D. Calhoun 117, 118, 2 Dara M. Cannon 119, 2 Gianpiero L. Cavalleri 120, 2 Ching-Yu Cheng 121, 2 Sven Cichon 60, 61, 122, 123, 2 Mark Cookson 124, 2 Aiden Corvin 125, 126, 2 Benedicto Crespo-Facorro 71, 2 Joanne E. Curran 2 Michael Czisch 127, 2 Anders M. Dale 2 Gareth E. Davies 128, 2 Anton J. M. De Craen 2 Eco J. C. De Geus 2 Philip L. De Jager 129, 130, 131, 2 Greig I. De Zubicaray 132, 2 Ian Deary 2 Stéphanie Debette 133, 2 Charles Decarli 2 Norman Delanty 13, 134, 2 Chantal Depondt 135, 2 Anita Destefano 27, 2 Allissa Dillman 136, 2 Srdjan Djurovic 2 Gary Donohoe 125, 119, 2 Wayne C. Drevets 119, 2 Ravi Duggirala 107, 2 Thomas Dyer 107, 108, 2 Christian Enzinger 2 Susanne Erk 137, 2 Thomas Espeseth 23, 95, 2 Iryna O. Fedko 138, 2 Guillén Fernández 139, 2 Luigi Ferrucci 5, 2 Simon Fisher 140, 2 Debra A. Fleischman 141, 142, 17, 2 Ian Ford 143, 2 Myriam Fornage 144, 145, 2 Tatiana M. Foroud 146, 2 Peter Fox 147, 2 Clyde Francks 32, 43, 2 Masaki Fukunaga 148, 2 J. Raphael Gibbs 149, 2 David C. Glahn 82, 2 Randy L. Gollub 150, 2 Harald H. H. Göring 151, 2 Robert Green 152, 2 Oliver Gruber 153, 2 Vilmundur Gudnason 154, 155, 2 Sebastian Guelfi 87, 2 Asta K. Håberg 2 Narelle K. Hansell 57, 2 John Hardy 156, 2 Catharina A. Hartman 57, 2 Ryota Hashimoto 2 Katrin Hegenscheid 157, 2 Andreas Heinz 2 Stephanie Le Hellard 39, 40, 2 Dena G. Hernandez 2 Dirk J. Heslenfeld 157, 2 Beng-Choon Ho 158, 2 Pieter J. Hoekstra 159, 2 Wolfgang Hoffmann 2 Albert Hofman 2 Florian Holsboer 160, 2 Georg Homuth 161, 2 Norbert Hosten 157, 2 Jouke-Jan Hottenga 2 Matthew Huentelman 162, 2 Hilleke E. Hulshoff Pol 2 Masashi Ikeda 2 Clifford R. Jack Jr 2 Mark Jenkinson 163, 2 Robert Johnson 164, 165, 2 Erik G. Jönsson 166, 2 J. Wouter Jukema 2 René S. Kahn 167, 2 Ryota Kanai 168, 169, 2 Iwona Kloszewska 170, 2 David S. Knopman 171, 2 Peter Kochunov 172, 2 John B. Kwok 173, 2 Stephen M. Lawrie 174, 2 Hervé Lemaître 175, 2 Xinmin Liu 2 Dan L. Longo 176, 2 Oscar L. Lopez 2 Simon Lovestone 177, 2 Oliver Martinez 2 Jean-Luc Martinot 178, 2 Venkata S. Mattay 179, 2 Colm Mcdonald 180, 2 Andrew Mcintosh 181, 2 Francis J. Mcmahon 2 Katie L. Mcmahon 182, 2 Patrizia Mecocci 183, 2 Ingrid Melle 100, 184, 185, 186, 2 Andreas Meyer-Lindenberg 187, 2 Sebastian Mohnke 188, 2 Grant W. Montgomery 189, 190, 2 Derek W. Morris 2 Thomas H. Mosley 191, 192, 2 Thomas W. Mühleisen 60, 61, 2 Bertram Müller-Myhsok 193, 2 Michael A. Nalls 194, 2 Matthias Nauck 195, 2 Thomas E. Nichols 196, 2 Wiro J. Niessen 197, 198, 2 Markus M. Nöthen 199, 2 Lars Nyberg 200, 2 Kazutaka Ohi 201, 2 Rene L. Olvera 202, 2 Roel A. Ophoff 203, 2 Massimo Pandolfo 135, 2 Tomas Paus 204, 205, 2 Zdenka Pausova 206, 2 Brenda W. J. H. Penninx 189, 2 G. Bruce Pike 5, 2 Steven G. Potkin 207, 2 Bruce M. Psaty 2 Simone Reppermund 110, 2 Marcella Rietschel 208, 209, 2 Joshua L. Roffman 210, 2 Nina Romanczuk-Seiferth 188, 2 Jerome I. Rotter 211, 2 Mina Ryten 87, 212, 2 Ralph L. Sacco 213, 2 Perminder S. Sachdev 2 Andrew Saykin 64, 66, 188, 2 Reinhold Schmidt 214, 2 Helena Schmidt 215, 2 Peter R. Schofield 216, 2 Sigurdur Sigursson 5, 2 Andrew Simmons 2 Andrew Singleton 194, 2 Sanjay M. Sisodiya 2 Colin Smith 2 Jordan W. Smoller 217, 2 Hilkka Soininen 218, 2 Vidar M. Steen 39, 2 David J. Stott 2 Jessika E. Sussmann 174, 2 Anbupalam Thalamuthu 219, 2 Arthur W. Toga 45, 2 Bryan J. Traynor 220, 2 Juan Troncoso 2 Magda Tsolaki 221, 2 Christophe Tzourio 222, 223, 2 Andre G. Uitterlinden 2 Maria C. Valdés Hernández 2 Marcel Van Der Brug 224, 2 Aad Van Der Lugt 225, 2 Nic J. A. Van Der Wee 226, 2 Neeltje E. M. Van Haren 11, 2 Dennis Van ’t Ent 2 Marie-Jose Van Tol 227, 2 Badri N. Vardarajan 2 Bruno Vellas 228, 2 Dick J. Veltman 63, 2 Henry Völzke 229, 2 Henrik Walter 230, 231, 2 Joanna M. Wardlaw 2 Thomas H. Wassink 232, 2 Michael E. Weale 233, 2 Daneil R Weinberger 2 Michael W. Weiner 2 Wei Wen 2 Eric Westman 234, 2 Tonya White 2 Tien Y. Wong 2 Clinton B. Wright 235, 2 Ronald H. Zielke 5, 2 Alan B. Zonderman 236, 2 Nicholas G. Martin 2 Cornelia M. Van Duijn 237, 2 Margaret J. Wright 238, 2 W. T. Longstreth 5, 2 Gunter Schumann 2 Hans J. Grabe 239, 2 Barbara Franke 240, 2 Lenore J. Launer 5, 2 Sarah E. Medland 83, 2 Sudha Seshadri 2 Paul M. Thompson 241, 2 M. Arfan Ikram 2
36 GIN - IMN UMR 5293 CNRS CEA Université de Bordeaux
IMN - Institut des Maladies Neurodégénératives [Bordeaux]
153 SARDES - System architecture for reflective distributed computing environments
Inria Grenoble - Rhône-Alpes, LIG - Laboratoire d'Informatique de Grenoble
227 LUMC
Abstract : The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r g ¼ À 0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
Type de document :
Article dans une revue
Nature Communications, Nature Publishing Group, 2017, 8, pp.13624. 〈10.1038/ncomms13624〉
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Derrek P. Hibar, Hieab H. H. Adams, Neda Jahanshad, Ganesh Chauhan, Jason L. Stein, et al.. Novel genetic loci associated with hippocampal volume. Nature Communications, Nature Publishing Group, 2017, 8, pp.13624. 〈10.1038/ncomms13624〉. 〈hal-01488337〉

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