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

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

Journal Article (2016)

Author(s)

Hieab H H Adams (Erasmus MC)

Derrek P. Hibar (Keck School of Medicine of USC)

Vincent Chouraki (Framingham Heart Study)

Jason L. Stein (University of North Carolina)

Paul A. Nyquist (Johns Hopkins University)

Miguel E. Rentería (Queensland Institute of Medical Research)

Stella Trompet (Leiden University Medical Center)

Alejandro Arias-Vasquez (Radboud Universiteit Nijmegen)

Sudha Seshadri (Framingham Heart Study)

Sylvane Desrivières (King’s College London)

Ashley H. Beecham (University of Miami)

Neda Jahanshad (Keck School of Medicine of USC)

Katharina Wittfeld (University Medicine Greifswald)

Sven J. Van Der Lee (Erasmus MC)

Lucija Abramovic ( University Medical Centre Utrecht)

Saud Alhusaini (Royal College of Surgeons in Ireland)

Najaf Amin (Erasmus MC)

Micael Andersson (Umeå University)

Konstantinos Arfanakis (Rush University Medical Center)

Benjamin S. Aribisala (The University of Edinburgh)

Nicola J. Armstrong (Murdoch University)

Lavinia Athanasiu (Oslo University Hospital)

Tomas Axelsson (Uppsala University)

Alexa Beiser (Harvard T.H. Chan School of Public Health)

Manon Bernard (University of Toronto)

Joshua C. Bis (University of Washington)

Laura M E Blanken (Erasmus MC)

Susan H. Blanton (University of Miami)

Marc M. Bohlken ( University Medical Centre Utrecht)

Marco P. Boks ( University Medical Centre Utrecht)

Janita Bralten (Radboud Universiteit Nijmegen)

Adam M. Brickman (Columbia University)

Owen Carmichael (Pennington Biomedical Research Center)

M. Mallar Chakravarty (McGill University)

Ganesh Chauhan

Qiang Chen (Lieber Institute for Brain Development)

Christopher R K Ching (UCLA School of Medicine)

Gabriel Cuellar-Partida (Queensland Institute of Medical Research)

Anouk Den Braber (Amsterdam UMC)

Nhat Trung Doan (Universitetet i Oslo)

Stefan Ehrlich (Massachusetts General Hospital)

Irina Filippi (APHP)

Tian Ge (Broad Institute of MIT and Harvard)

Sudheer Giddaluru (Haukeland University Hospital)

Aaron L. Goldman (Lieber Institute for Brain Development)

Rebecca F. Gottesman (Johns Hopkins University)

Corina U. Greven (Medical Research Council)

Oliver Grimm (University Heidelberg)

Michael E. Griswold (University of Mississippi Medical Center)

Tulio Guadalupe (International Max Planck Research School for Language Sciences)

Johanna Hass (Technische Universität Dresden)

Unn K. Haukvik (Diakonhjemmet Hospital)

Saima Hilal (National University Health System)

Edith Hofer

David Hoehn (Neuroimaging Research Group)

Avram J. Holmes (Yale University)

Martine Hoogman (Radboud Universiteit Nijmegen)

Deborah Janowitz (University Medicine Greifswald)

Tianye Jia (King’s College London)

Dalia Kasperaviciute (Imperial College London)

Sungeun Kim (Indiana University)

Marieke Klein (Radboud Universiteit Nijmegen)

Bernd Kraemer (University of Heidelberg)

Phil H. Lee

Jiemin Liao (Singapore Eye Research Institute)

David C M Liewald (The University of Edinburgh)

Lorna M. Lopez (The University of Edinburgh)

Michelle Luciano (The University of Edinburgh)

Christine Macare (King’s College London)

Andre Marquand (Radboud Universiteit Nijmegen)

Mar Matarin (University College London)

Karen A. Mather (University of New South Wales)

Manuel Mattheisen (Aarhus University)

Bernard Mazoyer (CEA)

David R. McKay (Olin Neuropsychiatric Research Center)

Rebekah McWhirter (University of Tasmania)

Yuri Milaneschi (Amsterdam UMC)

Nazanin Mirza-Schreiber (Neuroimaging Research Group)

Ryan L. Muetzel (Erasmus MC)

Susana Muñoz Maniega (The University of Edinburgh)

Kwangsik Nho (Indiana University)

Allison C. Nugent (National Institute of Mental Health)

Loes M Olde Loohuis (University of California)

Jaap Oosterlaan (Vrije Universiteit Amsterdam)

Martina Papmeyer (University of Bern)

Irene Pappa ( Erasmus Universiteit Rotterdam)

Lukas Pirpamer

Sara Pudas (Umeå University)

Benno Pütz (Neuroimaging Research Group)

Kumar B. Rajan (Rush University Medical Center)

Adaikalavan Ramasamy (University of Oxford)

Jennifer S. Richards (Radboud Universiteit Nijmegen)

Shannon L. Risacher (Indiana University)

Roberto Roiz-Santiañez (Cibersam (Centro Investigación Biomédica en Red Salud Mental))

Nanda Rommelse (Radboud Universiteit Nijmegen)

Emma J. Rose (Trinity College Dublin)

Natalie A. Royle (The University of Edinburgh)

Tatjana Rundek (University of Miami)

Philipp G. Sämann (Neuroimaging Research Group)

Claudia L. Satizabal (Boston University School of Medicine)

Lianne Schmaal (Framingham Heart Study)

Andrew J. Schork (Amsterdam UMC)

Li Shen (University of California)

Jean Shin (Indiana University)

Elena Shumskaya (University of Toronto)

Albert V. Smith (Radboud Universiteit Nijmegen)

Emma Sprooten (University of Iceland)

Lachlan T. Strike (Icahn School of Medicine at Mount Sinai)

Alexander Teumer (University of Queensland)

Russell Thomson (University Medicine Greifswald)

Diana Tordesillas-Gutierrez (Western Sydney University)

Roberto Toro (Valdecilla Biomedical Research Institute IDIVAL)

Daniah Trabzuni (Institut Pasteur, Paris)

Dhananjay Vaidya (King Faisal Specialist Hospital and Research Centre)

Jeroen Van Der Grond (Johns Hopkins University)

Dennis Van Der Meer (Leiden University Medical Center)

Marjolein M J Van Donkelaar (University Medical Center Groningen)

Kristel R. Van Eijk (Radboud Universiteit Nijmegen)

Theo G M Van Erp ( University Medical Centre Utrecht)

Daan Van Rooij (University of California)

Esther Walton (University Medical Center Groningen)

Lars T. Westlye (Technische Universität Dresden)

Christopher D. Whelan (Universitetet i Oslo)

Beverly G. Windham (Royal College of Surgeons in Ireland)

Anderson M. Winkler (University of Mississippi Medical Center)

Girma Woldehawariat (University of Oxford)

Christiane Wolf (Julius-Maximilians-Universität Würzburg)

Thomas Wolfers (Radboud Universiteit Nijmegen)

Bing Xu (King’s College London)

Lisa R. Yanek (Johns Hopkins University)

Jingyun Yang (Rush University Medical Center)

Alex Zijdenbos (Biospective Inc)

Marcel P. Zwiers (Radboud Universiteit Nijmegen)

Ingrid Agartz (Karolinska Institutet)

Neelum T. Aggarwal (Rush University Medical Center)

Laura Almasy (Children's Hospital of Philadelphia)

David Ames (University of Melbourne)

Philippe Amouyel (Université de Lille)

Ole A. Andreassen (Oslo University Hospital)

Sampath Arepalli (National Institute on Aging)

Amelia A. Assareh (University of New South Wales)

Sandra Barral (Columbia University)

Mark E. Bastin (The University of Edinburgh)

Diane M. Becker (Johns Hopkins University)

James T. Becker (University of Pittsburgh)

David A. Bennett (Rush University Medical Center)

John Blangero (University of Texas Rio Grande Valley School of Medicine)

Hans Van Bokhoven (Radboud Universiteit Nijmegen)

Dorret I. Boomsma (Amsterdam UMC)

Henry Brodaty (University of New South Wales)

Rachel M. Brouwer ( University Medical Centre Utrecht)

Han G. Brunner (Maastricht University Medical Center)

Randy L. Buckner (Harvard University)

Jan K. Buitelaar (Radboud Universiteit Nijmegen)

Kazima B. Bulayeva (Dagestan State University)

Wiepke Cahn ( University Medical Centre Utrecht)

Vince D. Calhoun (University of New Mexico)

Dara M. Cannon (National University of Ireland Galway)

Gianpiero L. Cavalleri (Royal College of Surgeons in Ireland)

Christopher Chen (National University Health System)

Ching Yu Cheng (Yong Loo Lin School of Medicine)

Sven Cichon (Forschungszentrum Jülich)

Mark R. Cookson (National Institute on Aging)

Aiden Corvin (Trinity College Dublin)

Benedicto Crespo-Facorro (Cibersam (Centro Investigación Biomédica en Red Salud Mental))

Joanne E. Curran (University of Texas Rio Grande Valley School of Medicine)

Michael Czisch (Neuroimaging Research Group)

Anders M. Dale (University of California)

Gareth E. Davies (Broad Institute of MIT and Harvard)

Eco J C De Geus (Amsterdam UMC)

Philip L. De Jager (Queensland University of Technology)

Greig I. De Zubicaray (Beaumont Hospital, Dublin)

Norman Delanty (Vrije Universiteit Brussel)

Chantal Depondt (Oslo University Hospital)

Anita L. Destefano (Haukeland University Hospital)

Allissa Dillman (National Institute on Aging)

Srdjan Djurovic (National University of Ireland Galway)

Gary Donohoe

Wayne C. Drevets (Charité Universittsmedizin Berlin)

Ravi Duggirala (University of Texas Rio Grande Valley School of Medicine)

Thomas D. Dyer (University of Texas Rio Grande Valley School of Medicine)

Susanne Erk (National Institute on Aging)

Thomas Espeseth (Universitetet i Oslo)

Denis A. Evans (Rush University Medical Center)

Iryna O. Fedko (Amsterdam UMC)

Guillén Fernández (Radboud Universiteit Nijmegen)

Luigi Ferrucci (Rush University Medical Center)

Simon E. Fisher (Max Planck Institute for Psycholinguistics)

Debra A. Fleischman (Indiana University)

Ian Ford (University of Texas Health Science Center at San Antonio)

Tatiana M. Foroud (National Institute for Physiological Sciences)

Peter T. Fox (Brigham and Women's Hospital)

Clyde Francks (Max Planck Institute for Psycholinguistics)

Masaki Fukunaga (Osaka University Graduate School of Medicine)

J. Raphael Gibbs (National Institute on Aging)

David C. Glahn (Olin Neuropsychiatric Research Center)

Randy L. Gollub (Harvard Medical School)

Harald H H Göring (University of Texas Rio Grande Valley School of Medicine)

Hans J. Grabe (University Medicine Greifswald)

Robert C. Green (Osaka University)

Oliver Gruber (University of Heidelberg)

Vilmundur Gudnason (University of Iceland)

Sebastian Guelfi (University College London)

Narelle K. Hansell (University of Queensland)

John Hardy (University College London)

Catharina A. Hartman (University Medical Center Groningen)

Ryota Hashimoto (German Center for Neurodegenerative Diseases (DZNE))

Katrin Hegenscheid (Vrije Universiteit Amsterdam)

Andreas Heinz (National Institute on Aging)

Stephanie Le Hellard (Haukeland University Hospital)

Dena G. Hernandez (University of Iowa)

Dirk J. Heslenfeld (HMNC Brain Health)

Beng Choon Ho (University Medicine Greifswald)

Pieter J. Hoekstra (University Medical Center Groningen)

Wolfgang Hoffmann (University Medicine Greifswald)

Albert Hofman (Erasmus MC)

Florian Holsboer (Fujita Health University)

Georg Homuth (Mayo Clinic)

Norbert Hosten (Vrije Universiteit Amsterdam)

Jouke Jan Hottenga (Amsterdam UMC)

Hilleke E Hulshoff Pol ( University Medical Centre Utrecht)

Masashi Ikeda (University of Maryland)

M. Kamran Ikram (Duke-NUS Graduate Medical School)

Clifford R. Jack (University of Sussex)

Mark Jenkinson (University of Oxford)

Robert Johnson (University College London)

Erik G. Jönsson (University of Oxford)

J. Wouter Jukema (Leiden University Medical Center)

René S. Kahn ( University Medical Centre Utrecht)

Derek W. Morris (Janssen)

Wiro J. Niessen (Erasmus MC)

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DOI related publication

https://doi.org/10.1038/nn.4398 Final published version

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https://resolver.tudelft.nl/uuid:94a9a1fd-dfbf-4484-8291-9e1caa490ccb

More Info

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Publication Year

2016

Language

English

Journal title

Nature Neuroscience

Issue number

12

Volume number

19

Pages (from-to)

1569-1582

Downloads counter

817

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 (genetic = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (N combined = 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.