Novel genetic loci associated with hippocampal volume
Authors: Hibar Derrek P. , Adams Hieab H. H. , Jahanshad Neda , Chauhan Ganesh , Stein Jason L. , Hofer Edith , Renteria Miguel E. , Bis Joshua C. , Arias-Vasquez Alejandro , Ikram M. Kamran , Desrivières Sylvane , Vernooij Meike W. , Abramovic Lucija , Alhusaini Saud , Amin Najaf , Andersson Micael , Arfanakis Konstantinos , Aribisala Benjamin S. , Armstrong Nicola J. , Athanasiu Lavinia , Axelsson Tomas , Beecham Ashley H. , Beiser Alexa , Bernard Manon , Blanton Susan H. , Bohlken Marc M. , Boks Marco P. , Bralten Janita , Brickman Adam M. , Carmichael Owen , Chakravarty M. Mallar , Chen Qiang , Ching Christopher R. K. , Chouraki Vincent , Cuellar-Partida Gabriel , Crivello Fabrice , Den Braber Anouk , Doan Nhat Trung , Ehrlich Stefan , Giddaluru Sudheer , Goldman Aaron L. , Gottesman Rebecca F. , Grimm Oliver , Griswold Michael E. , Guadalupe Tulio , Gutman Boris A. , Hass Johanna , Haukvik Unn K. , Hoehn David , Holmes Avram J. , Hoogman Martine , Janowitz Deborah , Jia Tianye , Jørgensen Kjetil N. , Karbalai Nazanin , Kasperaviciute Dalia , Kim Sungeun , Klein Marieke , Kraemer Bernd , Lee Phil H. , Liewald David C. M. , Lopez Lorna M. , Luciano Michelle , Macare Christine , Marquand Andre F. , Matarin Mar , Mather Karen A. , Mattheisen Manuel , McKay David R. , Milaneschi Yuri , Muñoz Maniega Susana , Nho Kwangsik , Nugent Allison C. , Nyquist Paul , Loohuis Loes M. Olde , Oosterlaan Jaap , Papmeyer Martina , Pirpamer Lukas , Pütz Benno , Ramasamy Adaikalavan , Richards Jennifer S. , Risacher Shannon L. , Roiz-Santiañez Roberto , Rommelse Nanda , Ropele Stefan , Rose Emma J. , Royle Natalie A. , Rundek Tatjana , Sämann Philipp G. , Saremi Arvin , Satizabal Claudia L. , Schmaal Lianne , Schork Andrew J. , Shen Li , Shin Jean , Shumskaya Elena , Smith Albert V. , Sprooten Emma , Strike Lachlan T. , Teumer Alexander , Tordesillas-Gutierrez Diana , Toro Roberto , Trabzuni Daniah , Trompet Stella , Vaidya Dhananjay , Van der Grond Jeroen , Van der Lee Sven J. , Van der Meer Dennis , Van Donkelaar Marjolein M. J. , Van Eijk Kristel R. , Van Erp Theo G. M. , Van Rooij Daan , Walton Esther , Westlye Lars T. , Whelan Christopher D. , Windham Beverly G. , Winkler Anderson M. , Wittfeld Katharina , Woldehawariat Girma , Wolf Christiane , Wolfers Thomas , Yanek Lisa R. , Yang Jingyun , Zijdenbos Alex , Zwiers Marcel P. , Agartz Ingrid , Almasy Laura , Ames David , Amouyel Philippe , Andreassen Ole A. , Arepalli Sampath , Assareh Amelia A. , Barral Sandra , Bastin Mark E. , Becker Diane M. , Becker James T. , Bennett David A. , Blangero John , van Bokhoven Hans , Boomsma Dorret I. , Brodaty Henry , Brouwer Rachel M. , Brunner Han G. , Buckner Randy L. , Buitelaar Jan K. , Bulayeva Kazima B. , Cahn Wiepke , Calhoun Vince D. , Cannon Dara M. , Cavalleri Gianpiero L. , Cheng Ching-Yu , Cichon Sven , Cookson Mark R. , Corvin Aiden , Crespo-Facorro Benedicto , Curran Joanne E. , Czisch Michael , Dale Anders M. , Davies Gareth E. , De Craen Anton J. M. , De Geus Eco J. C. , De Jager Philip L. , De Zubicaray Greig I. , Deary Ian J. , Debette Stéphanie , DeCarli Charles , Delanty Norman , Depondt Chantal , DeStefano Anita , Dillman Allissa , Djurovic Srdjan , Donohoe Gary , Drevets Wayne C. , Duggirala Ravi , Dyer Thomas D. , Enzinger Christian , Erk Susanne , Espeseth Thomas , Fedko Iryna O. , Fernández Guillén , Ferrucci Luigi , Fisher Simon E. , Fleischman Debra A. , Ford Ian , Fornage Myriam , Foroud Tatiana M. , Fox Peter T. , Francks Clyde , Fukunaga Masaki , Gibbs J. Raphael , Glahn David C. , Gollub Randy L. , Göring Harald H. H. , Green Robert C. , Gruber Oliver , Gudnason Vilmundur , Guelfi Sebastian , Håberg Asta K. , Hansell Narelle K. , Hardy John , Hartman Catharina A. , Hashimoto Ryota , Hegenscheid Katrin , Heinz Andreas , Le Hellard Stephanie , Hernandez Dena G. , Heslenfeld Dirk J. , Ho Beng-Choon , Hoekstra Pieter J. , Hoffmann Wolfgang , Hofman Albert , Holsboer Florian , Homuth Georg , Hosten Norbert , Hottenga Jouke-Jan , Huentelman Matthew , Hulshoff Pol Hilleke E. , Ikeda Masashi , Jack Jr Clifford R. , Jenkinson Mark , Johnson Robert , Jönsson Erik G. , Jukema J. Wouter , Kahn René S. , Kanai Ryota , Kloszewska Iwona , Knopman David S. , Kochunov Peter , Kwok John B. , Lawrie Stephen M. , Lemaître Hervé , Liu Xinmin , Longo Dan L. , Lopez Oscar L. , Lovestone Simon , Martinez Oliver , Martinot Jean-Luc , Mattay Venkata S. , McDonald Colm , McIntosh Andrew M. , McMahon Francis J. , McMahon Katie L. , Mecocci Patrizia , Melle Ingrid , Meyer-Lindenberg Andreas , Mohnke Sebastian , Montgomery Grant W. , Morris Derek W. , Mosley Thomas H. , Mühleisen Thomas W. , Müller-Myhsok Bertram , Nalls Michael A. , Nauck Matthias , Nichols Thomas E. , Niessen Wiro J. , Nöthen Markus M. , Nyberg Lars , Ohi Kazutaka , Olvera Rene L. , Ophoff Roel A. , Pandolfo Massimo , Paus Tomas , Pausova Zdenka , Penninx Brenda W. J. H. , Pike G. Bruce , Potkin Steven G. , Psaty Bruce M. , Reppermund Simone , Rietschel Marcella , Roffman Joshua L. , Romanczuk-Seiferth Nina , Rotter Jerome I. , Ryten Mina , Sacco Ralph L. , Sachdev Perminder S. , Saykin Andrew J. , Schmidt Reinhold , Schmidt Helena , Schofield Peter R. , Sigursson Sigurdur , Simmons Andrew , Singleton Andrew , Sisodiya Sanjay M. , Smith Colin , Smoller Jordan W. , Soininen Hilkka , Steen Vidar M. , Stott David J. , Sussmann Jessika E. , Thalamuthu Anbupalam , Toga Arthur W. , Traynor Bryan J. , Troncoso Juan , Tsolaki Magda , Tzourio Christophe , Uitterlinden Andre G. , Hernández Maria C. Valdés , Van der Brug Marcel , van der Lugt Aad , van der Wee Nic J. A. , Van Haren Neeltje E. M. , van ’t Ent Dennis , Van Tol Marie-Jose , Vardarajan Badri N. , Vellas Bruno , Veltman Dick J. , Völzke Henry , Walter Henrik , Wardlaw Joanna M. , Wassink Thomas H. , Weale Michael E. , Weinberger Daniel R. , Weiner Michael W. , Wen Wei , Westman Eric , White Tonya , Wong Tien Y. , Wright Clinton B. , Zielke Ronald H. , Zonderman Alan B. , Martin Nicholas G. , Van Duijn Cornelia M. , Wright Margaret J. , Longstreth W. T. , Schumann Gunter , Grabe Hans J. , Franke Barbara , Launer Lenore J. , Medland Sarah E. , Seshadri Sudha , Thompson Paul M. , Ikram M. Arfan 
Published: January 2017

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 (rg=−0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.