Journal article
Common genetic variants influence human subcortical brain structures
Nature (London), Vol.520(7546), pp.224-229
04/09/2015
DOI: 10.1038/nature14101
PMCID: PMC4393366
PMID: 25607358
Abstract
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.
Details
- Title: Subtitle
- Common genetic variants influence human subcortical brain structures
- Creators
- Derrek P Hibar - University of Southern CaliforniaJason L Stein - University of Southern CaliforniaMiguel E Renteria - QIMR Berghofer Medical Research InstituteAlejandro Arias-Vasquez - Radboud University NijmegenSylvane Desrivières - King's College LondonNeda Jahanshad - University of Southern CaliforniaRoberto Toro - Institut PasteurKatharina Wittfeld - Universität GreifswaldLucija Abramovic - Utrecht UniversityMicael Andersson - Umeå UniversityBenjamin S Aribisala - University of EdinburghNicola J Armstrong - UNSW SydneyManon Bernard - University of TorontoMarc M Bohlken - Utrecht UniversityMarco P Boks - Utrecht UniversityJanita Bralten - Radboud University NijmegenAndrew A Brown - University of OsloM Mallar Chakravarty - McGill UniversityQiang Chen - School of Technical PhysicsChristopher R K Ching - University of Southern CaliforniaGabriel Cuellar-Partida - QIMR Berghofer Medical Research InstituteAnouk den Braber - Amsterdam Public HealthSudheer Giddaluru - University of BergenAaron L Goldman - PhysicoChimie des Processus de Combustion et de l'AtmosphèreOliver Grimm - Heidelberg UniversityTulio Guadalupe - Max Planck SocietyJohanna Hass - Technische Universität DresdenGirma Woldehawariat - National Institutes of HealthAvram J Holmes - Yale UniversityMartine Hoogman - Radboud University NijmegenDeborah Janowitz - Universitätsmedizin GreifswaldTianye Jia - King's College LondonSungeun Kim - Indiana UniversityMarieke Klein - Radboud University NijmegenBernd Kraemer - University of GöttingenPhil H Lee - Broad InstituteLoes M Olde Loohuis - University of California [Los Angeles]Michelle Luciano - University of EdinburghChristine Macare - King's College LondonKaren A Mather - UNSW SydneyManuel Mattheisen - Lundbeck (United States)Yuri Milaneschi - Vrije Universiteit AmsterdamKwangsik Nho - Indiana UniversityMartina Papmeyer - University of EdinburghAdaikalavan Ramasamy - University College LondonShannon L Risacher - Indiana UniversityRoberto Roiz-Santiañez - Centro de Investigación Biomédica en RedEmma J Rose - Trinity College DublinAlireza Salami - Umeå UniversityPhilipp G Sämann - Max Planck SocietyLianne Schmaal - Vrije Universiteit AmsterdamAndrew J Schork - University of California San DiegoJean Shin - University of TorontoLachlan T Strike - The University of QueenslandAlexander Teumer - Universitätsmedizin GreifswaldMarjolein M J van Donkelaar - Radboud University NijmegenKristel R van Eijk - Utrecht UniversityRaymond K Walters - Broad InstituteLars T Westlye - University of OsloChristopher D Whelan - University of Southern CaliforniaAnderson M Winkler - Yale UniversityMarcel P Zwiers - Radboud University NijmegenSaud Alhusaini - McGill UniversityLavinia Athanasiu - University of OsloStefan Ehrlich - Technische Universität DresdenMarina M H Hakobjan - Radboud University Medical Center [Nijmegen]Cecilie B Hartberg - University of OsloUnn K Haukvik - University of OsloAngelien J G a M Heister - Radboud University Medical Center [Nijmegen]David Hoehn - Max Planck SocietyDalia Kasperaviciute - Epilepsy SocietyDavid C M Liewald - University of EdinburghLorna M Lopez - University of EdinburghRemco R R Makkinje - Radboud University NijmegenMar Matarin - University College LondonMarlies a M Naber - Radboud University Medical Center [Nijmegen]D Reese Mckay - Yale UniversityMargaret Needham - Trinity College DublinAllison C Nugent - National Institutes of HealthBenno Pütz - Max Planck SocietyNatalie A Royle - University of EdinburghLi Shen - Indiana UniversityEmma Sprooten - Yale UniversityDaniah Trabzuni - University College LondonSaskia S L van Der Marel - Radboud University NijmegenKimm J E van Hulzen - Radboud University NijmegenEsther Walton - Technische Universität DresdenChristiane Wolf - Max Planck SocietyLaura Almasy - The University of Texas Health Science Center at San AntonioDavid Ames - The University of MelbourneSampath Arepalli - National Institutes of HealthAmelia A Assareh - UNSW SydneyMark E Bastin - University of EdinburghHenry Brodaty - UNSW SydneyKazima B Bulayeva - Russian Academy of SciencesMelanie A Carless - Texas Biomedical Research InstituteSven Cichon - University of BaselAiden Corvin - Trinity College DublinJoanne E Curran - Texas Biomedical Research InstituteMichael Czisch - Max Planck SocietyEPIGEN
- Contributors
- Beng Choon Ho (Contributor) - University of Iowa, Psychiatry
- Resource Type
- Journal article
- Publication Details
- Nature (London), Vol.520(7546), pp.224-229
- DOI
- 10.1038/nature14101
- PMID
- 25607358
- PMCID
- PMC4393366
- NLM abbreviation
- Nature
- ISSN
- 0028-0836
- eISSN
- 1476-4687
- Publisher
- Nature Publishing Group
- Language
- English
- Date published
- 04/09/2015
- Academic Unit
- Psychiatry
- Record Identifier
- 9984280867102771
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