Common genetic variants influence human subcortical brain structures.

Authors:
Anderson Winkler
Anderson Winkler
Yale University School of Medicine
United States
Dr Kazima Bulayeva, PhD, DrSc
Dr Kazima Bulayeva, PhD, DrSc
VIGG RAS
Leading Scientist
human population genetics
Moscow | Russia
Mark Jenkinson
Mark Jenkinson
University of Oxford
Professor of Neuroimaging
Neuroimaging
Oxford, Oxfordshire | United Kingdom
Derrek P Hibar Jason L Stein Miguel E Renteria Alejandro Arias-Vasquez Sylvane Desrivières Neda Jahanshad Roberto Toro Katharina Wittfeld Lucija Abramovic Micael Andersson Benjamin S Aribisala Nicola J Armstrong Manon Bernard Marc M Bohlken Marco P Boks Janita Bralten Andrew A Brown M Mallar Chakravarty Qiang Chen Christopher R K Ching Gabriel Cuellar-Partida Anouk den Braber Sudheer Giddaluru Aaron L Goldman Oliver Grimm Tulio Guadalupe Johanna Hass Girma Woldehawariat Avram J Holmes Martine Hoogman Deborah Janowitz Tianye Jia Sungeun Kim Marieke Klein Bernd Kraemer Phil H Lee Loes M Olde Loohuis Michelle Luciano Christine Macare Karen A Mather Manuel Mattheisen Yuri Milaneschi Kwangsik Nho Martina Papmeyer Adaikalavan Ramasamy Shannon L Risacher Roberto Roiz-Santiañez Emma J Rose Alireza Salami Philipp G Sämann Lianne Schmaal Andrew J Schork Jean Shin Lachlan T Strike Alexander Teumer Marjolein M J van Donkelaar Kristel R van Eijk Raymond K Walters Lars T Westlye Christopher D Whelan Anderson M Winkler Marcel P Zwiers Saud Alhusaini Lavinia Athanasiu Stefan Ehrlich Marina M H Hakobjan Cecilie B Hartberg Unn K Haukvik Angelien J G A M Heister David Hoehn Dalia Kasperaviciute David C M Liewald Lorna M Lopez Remco R R Makkinje Mar Matarin Marlies A M Naber D Reese McKay Margaret Needham Allison C Nugent Benno Pütz Natalie A Royle Li Shen Emma Sprooten Daniah Trabzuni Saskia S L van der Marel Kimm J E van Hulzen Esther Walton Christiane Wolf Laura Almasy David Ames Sampath Arepalli Amelia A Assareh Mark E Bastin Henry Brodaty Kazima B Bulayeva Melanie A Carless Sven Cichon Aiden Corvin Joanne E Curran Michael Czisch Greig I de Zubicaray Allissa Dillman Ravi Duggirala Thomas D Dyer Susanne Erk Iryna O Fedko Luigi Ferrucci Tatiana M Foroud Peter T Fox Masaki Fukunaga J Raphael Gibbs Harald H H Göring Robert C Green Sebastian Guelfi Narelle K Hansell Catharina A Hartman Katrin Hegenscheid Andreas Heinz Dena G Hernandez Dirk J Heslenfeld Pieter J Hoekstra Florian Holsboer Georg Homuth Jouke-Jan Hottenga Masashi Ikeda Clifford R Jack Robert Johnson Ryota Kanai Maria Keil Jack W Kent Peter Kochunov John B Kwok Stephen M Lawrie Xinmin Liu Dan L Longo Katie L McMahon Eva Meisenzahl Ingrid Melle Sebastian Mohnke Grant W Montgomery Jeanette C Mostert Thomas W Mühleisen Michael A Nalls Thomas E Nichols Lars G Nilsson Markus M Nöthen Kazutaka Ohi Rene L Olvera Rocio Perez-Iglesias G Bruce Pike Steven G Potkin Ivar Reinvang Simone Reppermund Marcella Rietschel Nina Romanczuk-Seiferth Glenn D Rosen Dan Rujescu Knut Schnell Peter R Schofield Colin Smith Vidar M Steen Jessika E Sussmann Anbupalam Thalamuthu Arthur W Toga Bryan J Traynor Juan Troncoso Jessica A Turner Maria C Valdés Hernández Dennis van 't Ent Marcel van der Brug Nic J A van der Wee Marie-Jose van Tol Dick J Veltman Thomas H Wassink Eric Westman Ronald H Zielke Alan B Zonderman David G Ashbrook Reinmar Hager Lu Lu Francis J McMahon Derek W Morris Robert W Williams Han G Brunner Randy L Buckner Jan K Buitelaar Wiepke Cahn Vince D Calhoun Gianpiero L Cavalleri Benedicto Crespo-Facorro Anders M Dale Gareth E Davies Norman Delanty Chantal Depondt Srdjan Djurovic Wayne C Drevets Thomas Espeseth Randy L Gollub Beng-Choon Ho Wolfgang Hoffmann Norbert Hosten René S Kahn Stephanie Le Hellard Andreas Meyer-Lindenberg Bertram Müller-Myhsok Matthias Nauck Lars Nyberg Massimo Pandolfo Brenda W J H Penninx Joshua L Roffman Sanjay M Sisodiya Jordan W Smoller Hans van Bokhoven Neeltje E M van Haren Henry Völzke Henrik Walter Michael W Weiner Wei Wen Tonya White Ingrid Agartz Ole A Andreassen John Blangero Dorret I Boomsma Rachel M Brouwer Dara M Cannon Mark R Cookson Eco J C de Geus Ian J Deary Gary Donohoe Guillén Fernández Simon E Fisher Clyde Francks David C Glahn Hans J Grabe Oliver Gruber John Hardy Ryota Hashimoto Hilleke E Hulshoff Pol Erik G Jönsson Iwona Kloszewska Simon Lovestone Venkata S Mattay Patrizia Mecocci Colm McDonald Andrew M McIntosh Roel A Ophoff Tomas Paus Zdenka Pausova Mina Ryten Perminder S Sachdev Andrew J Saykin Andy Simmons Andrew Singleton Hilkka Soininen Joanna M Wardlaw Michael E Weale Daniel R Weinberger Hieab H H Adams Lenore J Launer Stephan Seiler Reinhold Schmidt Ganesh Chauhan Claudia L Satizabal James T Becker Lisa Yanek Sven J van der Lee Maritza Ebling Bruce Fischl W T Longstreth Douglas Greve Helena Schmidt Paul Nyquist Louis N Vinke Cornelia M van Duijn Luting Xue Bernard Mazoyer Joshua C Bis Vilmundur Gudnason Sudha Seshadri M Arfan Ikram Nicholas G Martin Margaret J Wright Gunter Schumann Barbara Franke Paul M Thompson Sarah E Medland

Nature 2015 Apr 21;520(7546):224-9. Epub 2015 Jan 21.

QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia.

The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.

Download full-text PDF

Source
http://www.ed.ac.uk/files/atoms/files//enigma2_nature_main.p
Web Search
http://enigma.ini.usc.edu/wp-content/uploads/2015/07/ENIGMA-
Web Search
http://www.nature.com/doifinder/10.1038/nature14101
Publisher Site
http://dx.doi.org/10.1038/nature14101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4393366PMC
April 2015
174 Reads
175 Citations
42.351 Impact Factor

Publication Analysis

Top Keywords

genetic variants
16
variants influencing
8
subcortical brain
8
human brain
8
brain regions
8
intracranial volume
8
brain structures
8
common genetic
8
brain
7
variants
6
volume
5
specific volumetric
4
volumetric effects
4
variants specific
4
volume intracranial
4
hippocampal volume
4
effects brain
4
volume variants
4
intergenic locus
4
strongest effects
4

References

(Supplied by CrossRef)

GA Blokland et al.
Twin Res. Hum. Genet. 2012

AV Kravitz et al.
Nature 2010

RA Poldrack et al.
Nature 2001

M Pessiglione et al.
Nature 2006

JL Stein et al.
Nature Genet. 2012

MA Ikram et al.
Nature Genet. 2012

H Lango Allen et al.
Nature 2010

EK Speliotes et al.
Nature Genet. 2010

S van der Sluis et al.
PLoS Genet. 2013

J Kumar et al.
Science 1995

Similar Publications