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

Journal article (2016)

Authors

Hieab H. Adams Erasmus MC
D. P. Hibar Keck School of Medicine of USC
Ashley H. Beecham University of Miami
L. Schmaal Framingham Heart Study
Andrew J. Schork Amsterdam UMC
Li Shen University of California
Jean Shin Indiana University - Purdue University
Elena Shumskaya University of Toronto
Albert V. Smith Radboud Universiteit Nijmegen
Emma Sprooten University of Iceland
L. T. Strike Icahn School of Medicine at Mount Sinai
Alexander Teumer University of Queensland
Russell Thomson University Medicine Greifswald
Neda Jahanshad Keck School of Medicine of USC
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 Center Utrecht
Daan Van Rooij University of California
K. Wittfeld University Medicine Greifswald
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 University of Würzburg
Thomas Wolfers Radboud Universiteit Nijmegen
Bing Xu King’s College London
Lisa R. Yanek Johns Hopkins University
Sven J. van der Lee Erasmus MC
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
Lucija Abramovic University Medical Center Utrecht
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
Saud Alhusaini Royal College of Surgeons in Ireland
Rachel M. Brouwer University Medical Center 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 Center 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
Najaf Amin Erasmus MC
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
M. 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
Micael Andersson Umeå University
Philip L. De Jager Queensland University of Technology
G. 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
Wayne C. Drevets Charité Universittsmedizin Berlin
Ravi Duggirala University of Texas Rio Grande Valley School of Medicine
Konstantinos Arfanakis Rush University Medical Center
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 - Purdue University
Ian Ford University of Texas Health Science Center at San Antonio
Benjamin S. Aribisala The University of Edinburgh
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
H. J. Grabe University Medicine Greifswald
Chris Green Osaka University
Vincent Chouraki Framingham Heart Study
Nicola J. Armstrong Murdoch 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
Lavinia Athanasiu Oslo 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
Tomas Axelsson Uppsala University
Hilleke E. Hulshoff Pol University Medical Center 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 Center Utrecht
Derek W. Morris Janssen
Alexa Beiser Harvard T.H. Chan School of Public Health
W.J. Niessen Erasmus MC
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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 Center Utrecht
Marco P. Boks University Medical Center Utrecht
Jason L. Stein University of North Carolina
J. Bralten Radboud Universiteit Nijmegen
Adam M. Brickman Columbia University
Owen Carmichael Pennington Biomedical Research Center
M. Mallar Chakravarty McGill University
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
Paul A. Nyquist Johns Hopkins University
Stefan Ehrlich Massachusetts General Hospital
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
Miguel E. Rentería Queensland Institute of Medical Research
Johanna Hass Technische Universität Dresden
Unn K. Haukvik Diakonhjemmet Hospital
Saima Hilal National University Health System
D. 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
Stella Trompet Leiden University Medical Center
Sungeun Kim Indiana University - Purdue University
Marieke Klein Radboud Universiteit Nijmegen
Bernd Kraemer University of Heidelberg
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
Alejandro Arias-Vasquez Radboud Universiteit Nijmegen
Mar Matarin University College London
Karen A. Mather University of New South Wales
Manuel Mattheisen Aarhus University
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
Sudha Seshadri Framingham Heart Study
Kwangsik Nho Indiana University - Purdue 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
Sara Pudas Umeå University
Benno Pütz Neuroimaging Research Group
Kumar B. Rajan Rush University Medical Center
Sylvane Desrivières King’s College London
Adaikalavan Ramasamy University of Oxford
Jennifer S. Richards Radboud Universiteit Nijmegen
Shannon L. Risacher Indiana University - Purdue 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
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Published Date

2016

Language

English

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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.