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 2 Han G. Brunner 2 Randy L. Buckner 112, 2 Jan K. Buitelaar 113, 2 Kazima B. Bulayeva 114, 2 Wiepke Cahn 115, 2 Vince D. Calhoun 116, 117, 2 Dara M. Cannon 118, 2 Gianpiero L. Cavalleri 119, 2 Ching-Yu Cheng 120, 2 Sven Cichon 60, 61, 121, 122, 2 Mark Cookson 123, 2 Aiden Corvin 124, 125, 2 Benedicto Crespo-Facorro 71, 2 Joanne E. Curran 2 Michael Czisch 126, 2 Anders M. Dale 2 Gareth E. Davies 127, 2 Anton J. M. De Craen 2 Eco J. C. De Geus 2 Philip L. De Jager 128, 129, 130, 2 Greig I. De Zubicaray 131, 2 Ian Deary 2 Stéphanie Debette 132, 2 Charles Decarli 2 Norman Delanty 13, 133, 2 Chantal Depondt 134, 2 Anita Destefano 27, 2 Allissa Dillman 135, 2 Srdjan Djurovic 2 Gary Donohoe 124, 118, 2 Wayne C. Drevets 118, 2 Ravi Duggirala 107, 2 Thomas Dyer 107, 108, 2 Christian Enzinger 2 Susanne Erk 136, 2 Thomas Espeseth 23, 95, 2 Iryna O. Fedko 137, 2 Guillén Fernández 138, 2 Luigi Ferrucci 5, 2 Simon Fisher 139, 2 Debra A. Fleischman 140, 141, 17, 2 Ian Ford 142, 2 Myriam Fornage 143, 144, 2 Tatiana M. Foroud 145, 2 Peter Fox 146, 2 Clyde Francks 32, 43, 2 Masaki Fukunaga 147, 2 J. Raphael Gibbs 148, 2 David C. Glahn 82, 2 Randy L. Gollub 149, 2 Harald H. H. Göring 150, 2 Robert Green 151, 2 Oliver Gruber 152, 2 Vilmundur Gudnason 153, 154, 2 Sebastian Guelfi 87, 2 Asta K. Håberg 2 Narelle K. Hansell 57, 2 John Hardy 155, 2 Catharina A. Hartman 57, 2 Ryota Hashimoto 2 Katrin Hegenscheid 156, 2 Andreas Heinz 2 Stephanie Le Hellard 39, 40, 2 Dena G. Hernandez 2 Dirk J. Heslenfeld 156, 2 Beng-Choon Ho 157, 2 Pieter J. Hoekstra 158, 2 Wolfgang Hoffmann 2 Albert Hofman 2 Florian Holsboer 159, 2 Georg Homuth 160, 2 Norbert Hosten 156, 2 Jouke-Jan Hottenga 2 Matthew Huentelman 161, 2 Hilleke E. Hulshoff Pol 2 Masashi Ikeda 2 Clifford R. Jack Jr 2 Mark Jenkinson 162, 2 Robert Johnson 163, 164, 2 Erik G. Jönsson 165, 2 J. Wouter Jukema 2 René S. Kahn 166, 2 Ryota Kanai 167, 168, 2 Iwona Kloszewska 169, 2 David S. Knopman 170, 2 Peter Kochunov 171, 2 John B. Kwok 172, 2 Stephen M. Lawrie 173, 2 Hervé Lemaître 174, 2 Xinmin Liu 2 Dan L. Longo 175, 2 Oscar L. Lopez 2 Simon Lovestone 176, 2 Oliver Martinez 2 Jean-Luc Martinot 177, 2 Venkata S. Mattay 178, 2 Colm Mcdonald 179, 2 Andrew Mcintosh 180, 2 Francis J. Mcmahon 2 Katie L. Mcmahon 181, 2 Patrizia Mecocci 182, 2 Ingrid Melle 100, 183, 184, 185, 2 Andreas Meyer-Lindenberg 186, 2 Sebastian Mohnke 187, 2 Grant W. Montgomery 188, 189, 2 Derek W. Morris 2 Thomas H. Mosley 190, 191, 2 Thomas W. Mühleisen 60, 61, 2 Bertram Müller-Myhsok 192, 2 Michael A. Nalls 193, 2 Matthias Nauck 194, 2 Thomas E. Nichols 195, 2 Wiro J. Niessen 196, 197, 2 Markus M. Nöthen 198, 2 Lars Nyberg 199, 2 Kazutaka Ohi 200, 2 Rene L. Olvera 201, 2 Roel A. Ophoff 202, 2 Massimo Pandolfo 134, 2 Tomas Paus 203, 204, 2 Zdenka Pausova 205, 2 Brenda W. J. H. Penninx 188, 2 G. Bruce Pike 5, 2 Steven G. Potkin 206, 2 Bruce M. Psaty 2 Simone Reppermund 110, 2 Marcella Rietschel 207, 208, 2 Joshua L. Roffman 209, 2 Nina Romanczuk-Seiferth 187, 2 Jerome I. Rotter 210, 2 Mina Ryten 87, 211, 2 Ralph L. Sacco 212, 2 Perminder S. Sachdev 2 Andrew Saykin 64, 66, 187, 2 Reinhold Schmidt 213, 2 Helena Schmidt 214, 2 Peter R. Schofield 215, 2 Sigurdur Sigursson 5, 2 Andrew Simmons 2 Andrew Singleton 193, 2 Sanjay M. Sisodiya 2 Colin Smith 2 Jordan W. Smoller 216, 2 Hilkka Soininen 217, 2 Vidar M. Steen 39, 2 David J. Stott 2 Jessika E. Sussmann 173, 2 Anbupalam Thalamuthu 218, 2 Arthur W. Toga 45, 2 Bryan J. Traynor 219, 2 Juan Troncoso 2 Magda Tsolaki 220, 2 Christophe Tzourio 221, 222, 2 Andre G. Uitterlinden 2 Maria C. Valdés Hernández 2 Marcel Van Der Brug 223, 2 Aad Van Der Lugt 224, 2 Nic J. A. Van Der Wee 225, 2 Neeltje E. M. Van Haren 11, 2 Dennis Van ’t Ent 2 Marie-Jose Van Tol 226, 2 Badri N. Vardarajan 2 Bruno Vellas 227, 2 Dick J. Veltman 63, 2 Henry Völzke 228, 2 Henrik Walter 229, 230, 2 Joanna M. Wardlaw 2 Thomas H. Wassink 231, 2 Michael E. Weale 232, 2 Daneil R Weinberger 2 Michael W. Weiner 2 Wei Wen 2 Eric Westman 233, 2 Tonya White 2 Tien Y. Wong 2 Clinton B. Wright 234, 2 Ronald H. Zielke 5, 2 Alan B. Zonderman 235, 2 Nicholas G. Martin 2 Cornelia M. Van Duijn 236, 2 Margaret J. Wright 237, 2 W. T. Longstreth 5, 2 Gunter Schumann 2 Hans J. Grabe 238, 2 Barbara Franke 239, 2 Lenore J. Launer 5, 2 Sarah E. Medland 83, 2 Sudha Seshadri 2 Paul M. Thompson 240, 2 M. Arfan Ikram 2
36 GIN - IMN UMR 5293 CNRS CEA Université de Bordeaux
IMN - Institut des Maladies Neurodégénératives [Bordeaux]
152 SARDES - System architecture for reflective distributed computing environments
Inria Grenoble - Rhône-Alpes, LIG - Laboratoire d'Informatique de Grenoble
226 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.
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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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