Novel genetic loci associated with hippocampal volume.

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

Nat Commun 2017 01 18;8:13624. Epub 2017 Jan 18.

Department of Epidemiology, Erasmus University Medical Center, 3015 CE Rotterdam, The Netherlands.

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=-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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http://dx.doi.org/10.1038/ncomms13624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5253632PMC
January 2017
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