Identification of common variants associated with human hippocampal and intracranial volumes
Jason J Stein
(1)
,
Sarah Medland
(2)
,
Alejandro Arias Vasquez
(3)
,
Derrek D Hibar
(1)
,
Rudy E Senstad
(1)
,
Anderson M Winkler
(4)
,
Roberto Toro
(5)
,
Katja Appel
(6, 7)
,
Richard Bartecek
(8)
,
Ørjan Bergmann
(9)
,
Manon Bernard
(10)
,
Andrew A Brown
(9)
,
Dara D Cannon
(11)
,
M Mallar Chakravarty
(12)
,
Andrea Christoforou
(13)
,
Martin Domin
(6)
,
Oliver Grimm
(7)
,
Marisa Hollinshead
(14)
,
Avram J Holmes
(14)
,
Georg Homuth
(6)
,
Jouke-Jan Hottenga
(15)
,
Camilla Langan
(11)
,
Lorna Lopez
(16)
,
Narelle Hansell
(2)
,
Kristy S Hwang
(1)
,
Sungeun Kim
(17)
,
Gonzalo Laje
,
Phil Lee
(18)
,
Xinmin Liu
(19)
,
Eva Loth
(20)
,
Anbarasu Lourdusamy
(21)
,
Morten Mattingsdal
(9)
,
Sebastian Mohnke
,
Susana Muñoz Maniega
(16)
,
Kwangsik Nho
(1)
,
Allison C Nugent
,
Carol O'Brien
,
Martina Papmeyer
,
Benno Pütz
,
Adaikalavan Ramasamy
,
Jerod Rasmussen
,
Mark Rijpkema
(3)
,
Shannon L Risacher
(1)
,
J Cooper Cooper Roddey
,
Emma Rose
,
Mina Ryten
,
Li Shen
(1)
,
Emma Sprooten
,
Eric Strengman
,
Alexander Teumer
(6)
,
Daniah Trabzuni
,
Jessica Turner
(22)
,
Kristel van Eijk
(8)
,
Theo M van Erp
(23)
,
Marie-Jose van Tol
(24)
,
Katharina Wittfeld
(6)
,
Christiane Wolf
(25)
,
Saskia Woudstra
,
Andre Aleman
(26)
,
Saud Alhusaini
(27)
,
Laura Almasy
(28)
,
Elisabeth Binder
,
David G Brohawn
,
Rita Cantor
,
Melanie A Carless
,
Aiden Corvin
,
Michael Czisch
(29)
,
Joanne E Curran
,
Gail Davies
(16)
,
Marcio a A de Almeida
,
Norman Delanty
(30)
,
Chantal Depondt
,
Ravi Duggirala
,
Thomas Dyer
(31)
,
Susanne Erk
,
Jesen Fagerness
,
Peter Fox
(31)
,
Nelson B. Freimer
(32)
,
Michael Gill
,
Harald H H Göring
,
Donald J Hagler
,
David Hoehn
(33)
,
Florian Holsboer
,
Martine Hoogman
(3)
,
Norbert Hosten
(6)
,
Neda M Jahanshad
,
Matthew Johnson
(34)
,
Dalia Kasperaviciute
,
Jack Kent
(28)
,
Peter M Kochunov
,
Jack L Lancaster
,
Stephen M Lawrie
,
David C Liewald
(16)
,
René Mandl
(8)
,
Mar Matarin
,
Manuel Mattheisen
,
Eva Meisenzahl
,
Ingrid Melle
(9)
,
Eric K Moses
,
Thomas W. Mühleisen
,
Matthias Nauck
,
Markus M. Nöthen
,
Rene L Olvera
,
Massimo Pandolfo
,
G Bruce Pike
,
Ralf Puls
(6)
,
Ivar Reinvang
,
Miguel E Rentería
(2)
,
Marcella Rietschel
(7)
,
Joshua L Roffman
,
Natalie A Royle
(16)
,
Dan Rujescu
,
Jonathan Savitz
,
Hugo G Schnack
(8)
,
Knut Schnell
,
Nina Seiferth
,
Colin Smith
(35)
,
Vidar Steen
(13)
,
Maria C Valdés Hernández
(16)
,
Martijn D van den Heuvel
(8)
,
Nic J van Der Wee
,
Neeltje E M van Haren
(8)
,
Joris A Veltman
(3)
,
Henry Völzke
,
Robert Walker
,
Lars Westlye
,
Christopher D Whelan
,
Ingrid Agartz
(9)
,
Dorret Boomsma
(15)
,
Gianpiero L Cavalleri
,
Anders J Dale
,
Srdjan Djurovic
(9)
,
Wayne Drevets
,
Peter Hagoort
(3)
,
Jérémy Hall
,
Andreas Heinz
(36)
,
Clifford R Jack
,
Tatiana Foroud
,
Stephanie Le Hellard
(13)
,
Fabio Macciardi
(37)
,
Grant W. Montgomery
(2)
,
Jean Baptiste Poline
,
David Porteous
(16)
,
Sanjay Sisodiya
(38)
,
John M Starr
(16)
,
Jessika Sussmann
,
Arthur W. Toga
(1)
,
Dick J Veltman
,
Henrik Walter
,
Michael Weiner
(39)
,
Joshua Bis
(40)
,
M Arfan Ikram
(41)
,
Vilmundur Gudnason
,
Christophe Tzourio
,
Meike Vernooij
(2)
,
Lenore J Launer
,
Charles Decarli
,
Sudha Seshadri
,
Ole A. Andreassen
(9)
,
Liana G Apostolova
(1)
,
Mark Bastin
(16)
,
John Blangero
,
Han G. Brunner
(3)
,
Randy L Buckner
(14)
,
Sven Cichon
,
Giovanni Coppola
(42)
,
Greig G de Zubicaray
(43)
,
Ian Deary
(16)
,
Gary Donohoe
,
Eco de Geus
(15)
,
Thomas Espeseth
(9)
,
Guillén Fernández
(3)
,
David D Glahn
(44, 4)
,
Hans J Grabe
(6)
,
John Hardy
(45)
,
Derek Morris
,
Hilleke D Hulshoff Pol
(8)
,
Mark Jenkinson
,
Rene Kahn
(8)
,
Bertram Müller-Myhsok
,
Albert V. Smith
(46)
,
Colm Mcdonald
(11)
,
Andrew Mcintosh
,
Francis J. Mcmahon
,
Katie M Mcmahon
(47)
,
Andreas Meyer-Lindenberg
(7)
,
Thomas E Nichols
,
Roel A. Ophoff
(8)
,
Tomas Paus
(48)
,
Zdenka Pausova
(10)
,
Brenda Penninx
,
Steven G Potkin
,
Philipp G Sämann
,
Andrew Saykin
(1)
,
Gunter Schumann
(21)
,
Jordan W. Smoller
(49)
,
Joanna Wardlaw
(16)
,
Michael E Weale
,
Nicholas G Martin
(2)
,
Barbara Franke
(3)
,
Margaret Wright
(2)
,
Paul M. Thompson
(1)
1
David Geffen School of Medicine [Los Angeles]
2 Queensland Institute of Medical Research
3 Radboud University Medical Center [Nijmegen]
4 YSM - Yale School of Medicine [New Haven, Connecticut]
5 Génétique Humaine et Fonctions Cognitives
6 Universität Greifswald - University of Greifswald
7 Universität Heidelberg [Heidelberg] = Heidelberg University
8 University Medical Center [Utrecht]
9 UiO - University of Oslo
10 University of Toronto
11 NUI Galway - National University of Ireland [Galway]
12 Montreal Neurological Institute and Hospital
13 UiB - University of Bergen
14 Harvard University
15 VU - Vrije Universiteit Amsterdam [Amsterdam]
16 University of Edinburgh
17 SRSMC - Structure et Réactivité des Systèmes Moléculaires Complexes
18 BROAD INSTITUTE - Broad Institute of MIT and Harvard
19 NIH - National Institutes of Health [Bethesda]
20 Department of Forensic and Neurodevelopmental Sciences
21 Institute of Psychiatry, Psychology & Neuroscience, King's College London
22 Georgia State University
23 Department of Psychiatry and Human Behavior [Irvine]
24 LUMC - Leiden University Medical Center
25 Dundee Technopole
26 University of Groningen [Groningen]
27 Molecular and Cellular Therapeutics
28 Department of Genetics
29 Bijvoet Center of Biomolecular Research [Utrecht]
30 Neurology Division, Beaumont Hospital, Dublin 9, Ireland
31 UTHealth - The University of Texas Health Science Center at Houston
32 Center for Neurobehavioral Genetics
33 Max Planck Institute of Psychiatry
34 Department of Computer Science
35 UMR LSTM - Laboratoire des symbioses tropicales et méditerranéennes
36 Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]
37 UC Irvine - University of California [Irvine]
38 Institute of Neurology [London]
39 UC San Francisco - University of California [San Francisco]
40 Department of Medicine
41 Erasmus MC - Erasmus University Medical Center [Rotterdam]
42 Università degli Studi di Salermo
43 School of Psychology, University of Queensland
44 Hartford Hospital
45 Lancaster University
46 University of Iceland [Reykjavik]
47 Centre for Advanced Imaging
48 MNI - McConnell Brain Imaging Centre
49 Stanley Center for Psychiatric Research
2 Queensland Institute of Medical Research
3 Radboud University Medical Center [Nijmegen]
4 YSM - Yale School of Medicine [New Haven, Connecticut]
5 Génétique Humaine et Fonctions Cognitives
6 Universität Greifswald - University of Greifswald
7 Universität Heidelberg [Heidelberg] = Heidelberg University
8 University Medical Center [Utrecht]
9 UiO - University of Oslo
10 University of Toronto
11 NUI Galway - National University of Ireland [Galway]
12 Montreal Neurological Institute and Hospital
13 UiB - University of Bergen
14 Harvard University
15 VU - Vrije Universiteit Amsterdam [Amsterdam]
16 University of Edinburgh
17 SRSMC - Structure et Réactivité des Systèmes Moléculaires Complexes
18 BROAD INSTITUTE - Broad Institute of MIT and Harvard
19 NIH - National Institutes of Health [Bethesda]
20 Department of Forensic and Neurodevelopmental Sciences
21 Institute of Psychiatry, Psychology & Neuroscience, King's College London
22 Georgia State University
23 Department of Psychiatry and Human Behavior [Irvine]
24 LUMC - Leiden University Medical Center
25 Dundee Technopole
26 University of Groningen [Groningen]
27 Molecular and Cellular Therapeutics
28 Department of Genetics
29 Bijvoet Center of Biomolecular Research [Utrecht]
30 Neurology Division, Beaumont Hospital, Dublin 9, Ireland
31 UTHealth - The University of Texas Health Science Center at Houston
32 Center for Neurobehavioral Genetics
33 Max Planck Institute of Psychiatry
34 Department of Computer Science
35 UMR LSTM - Laboratoire des symbioses tropicales et méditerranéennes
36 Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]
37 UC Irvine - University of California [Irvine]
38 Institute of Neurology [London]
39 UC San Francisco - University of California [San Francisco]
40 Department of Medicine
41 Erasmus MC - Erasmus University Medical Center [Rotterdam]
42 Università degli Studi di Salermo
43 School of Psychology, University of Queensland
44 Hartford Hospital
45 Lancaster University
46 University of Iceland [Reykjavik]
47 Centre for Advanced Imaging
48 MNI - McConnell Brain Imaging Centre
49 Stanley Center for Psychiatric Research
Roberto Toro
- Function : Author
- PersonId : 172082
- IdHAL : robertotoro
- ORCID : 0000-0002-6671-858X
- IdRef : 089439317
Katja Appel
- Function : Author
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Gonzalo Laje
- Function : Author
Phil Lee
- Function : Author
- PersonId : 779324
- ORCID : 0000-0002-2087-8887
Sebastian Mohnke
- Function : Author
Allison C Nugent
- Function : Author
Carol O'Brien
- Function : Author
Martina Papmeyer
- Function : Author
Benno Pütz
- Function : Author
Adaikalavan Ramasamy
- Function : Author
Jerod Rasmussen
- Function : Author
J Cooper Cooper Roddey
- Function : Author
Emma Rose
- Function : Author
Mina Ryten
- Function : Author
Emma Sprooten
- Function : Author
Eric Strengman
- Function : Author
Daniah Trabzuni
- Function : Author
Saskia Woudstra
- Function : Author
Elisabeth Binder
- Function : Author
- PersonId : 763104
- ORCID : 0000-0001-7088-6618
David G Brohawn
- Function : Author
Rita Cantor
- Function : Author
Melanie A Carless
- Function : Author
Aiden Corvin
- Function : Author
- PersonId : 874866
Joanne E Curran
- Function : Author
Marcio a A de Almeida
- Function : Author
Chantal Depondt
- Function : Author
Ravi Duggirala
- Function : Author
Susanne Erk
- Function : Author
Jesen Fagerness
- Function : Author
Michael Gill
- Function : Author
Harald H H Göring
- Function : Author
Donald J Hagler
- Function : Author
Florian Holsboer
- Function : Author
Neda M Jahanshad
- Function : Author
Matthew Johnson
- Function : Author
- PersonId : 761710
- ORCID : 0000-0002-3645-3955
- IdRef : 166001775
Dalia Kasperaviciute
- Function : Author
Peter M Kochunov
- Function : Author
Jack L Lancaster
- Function : Author
Stephen M Lawrie
- Function : Author
Mar Matarin
- Function : Author
Manuel Mattheisen
- Function : Author
Eva Meisenzahl
- Function : Author
Eric K Moses
- Function : Author
Thomas W. Mühleisen
- Function : Author
Matthias Nauck
- Function : Author
Markus M. Nöthen
- Function : Author
Rene L Olvera
- Function : Author
Massimo Pandolfo
- Function : Author
G Bruce Pike
- Function : Author
Ivar Reinvang
- Function : Author
Marcella Rietschel
- Function : Author
- PersonId : 757743
- ORCID : 0000-0002-5236-6149
Joshua L Roffman
- Function : Author
Dan Rujescu
- Function : Author
Jonathan Savitz
- Function : Author
Knut Schnell
- Function : Author
Nina Seiferth
- Function : Author
Nic J van Der Wee
- Function : Author
Henry Völzke
- Function : Author
Robert Walker
- Function : Author
Lars Westlye
- Function : Author
Christopher D Whelan
- Function : Author
Gianpiero L Cavalleri
- Function : Author
Anders J Dale
- Function : Author
Wayne Drevets
- Function : Author
Jérémy Hall
- Function : Author
Clifford R Jack
- Function : Author
Tatiana Foroud
- Function : Author
Jean Baptiste Poline
- Function : Author
Jessika Sussmann
- Function : Author
Dick J Veltman
- Function : Author
Henrik Walter
- Function : Author
- PersonId : 879223
Vilmundur Gudnason
- Function : Author
Christophe Tzourio
- Function : Author
- PersonId : 758563
- ORCID : 0000-0002-6517-2984
- IdRef : 069829209
Lenore J Launer
- Function : Author
Charles Decarli
- Function : Author
Sudha Seshadri
- Function : Author
John Blangero
- Function : Author
Sven Cichon
- Function : Author
- PersonId : 908270
Gary Donohoe
- Function : Author
Derek Morris
- Function : Author
Mark Jenkinson
- Function : Author
Bertram Müller-Myhsok
- Function : Author
- PersonId : 763103
- ORCID : 0000-0002-0719-101X
- IdRef : 152975233
Andrew Mcintosh
- Function : Author
Francis J. Mcmahon
- Function : Author
Thomas E Nichols
- Function : Author
Brenda Penninx
- Function : Author
Steven G Potkin
- Function : Author
Philipp G Sämann
- Function : Author
Michael E Weale
- Function : Author
Abstract
Identifying genetic variants influencing human brain structures may reveal new biological mechanisms underlying cognition and neuropsychiatric illness. The volume of the hippocampus is a biomarker of incipient Alzheimer's disease and is reduced in schizophrenia, major depression and mesial temporal lobe epilepsy. Whereas many brain imaging phenotypes are highly heritable, identifying and replicating genetic influences has been difficult, as small effects and the high costs of magnetic resonance imaging (MRI) have led to underpowered studies. Here we report genome-wide association meta-analyses and replication for mean bilateral hippocampal, total brain and intracranial volumes from a large multinational consortium. The intergenic variant rs7294919 was associated with hippocampal volume (12q24.22; N = 21,151; P = 6.70 × 10(-16)) and the expression levels of the positional candidate gene TESC in brain tissue. Additionally, rs10784502, located within HMGA2, was associated with intracranial volume (12q14.3; N = 15,782; P = 1.12 × 10(-12)). We also identified a suggestive association with total brain volume at rs10494373 within DDR2 (1q23.3; N = 6,500; P = 5.81 × 10(-7)).