Journal article
Novel genetic loci underlying human intracranial volume identified through genome-wide association
Nature neuroscience, Vol.19(12), pp.1569–1582-1582
12/2016
DOI: 10.1038/nn.4398
PMCID: PMC5227112
PMID: 27694991
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 (ρgenetic = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (Ncombined = 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.
Details
- Title: Subtitle
- Novel genetic loci underlying human intracranial volume identified through genome-wide association
- Creators
- Hieab H H Adams - Erasmus University RotterdamDerrek P Hibar - University of Southern CaliforniaVincent Chouraki - Boston University School of MedicineJason L Stein - University of Southern CaliforniaPaul A Nyquist - Johns Hopkins UniversityMiguel E Rentería - QIMR Berghofer Medical Research InstituteStella Trompet - Leiden UniversityAlejandro Arias-Vasquez - Radboud University NijmegenSudha Seshadri - Boston UniversitySylvane Desrivières - King's College LondonAshley H Beecham - University of MiamiNeda Jahanshad - University of Southern CaliforniaKatharina Wittfeld - Universität GreifswaldSven J. van der Lee - Erasmus University RotterdamLucija Abramovic - Utrecht UniversitySaud Alhusaini - McGill UniversityNajaf Amin - Erasmus University RotterdamMicael Andersson - Umeå UniversityKonstantinos Arfanakis - Illinois Institute of TechnologyBenjamin S Aribisala - University of EdinburghNicola J Armstrong - UNSW SydneyLavinia Athanasiu - University of OsloTomas Axelsson - Uppsala UniversityAlex Beiser - Boston University School of MedicineBernard Bernard - University of TorontoJoshua C Bis - University of WashingtonLaura Blanken - Erasmus University Medical Center [Rotterdam]Susan H Blanton - University of MiamiMar BohlkenMar BoksJanita Bralten - Radboud University NijmegenAdam M Brickman - Columbia UniversityOwen Carmichael - Pennington Biomedical Research CenterM Mallar Chakravarty - McGill UniversityGanesh Chauhan - Université de BordeauxQiang Chen - Lieber Institute for Brain DevelopmentChristophe Ching - Keck School of Medicine [Los Angeles]Gabriel Cuellar-Partida - QIMR Berghofer Medical Research InstituteAnouk Den Braber - Vrije Universiteit AmsterdamNhat Trung Doan - University of OsloStefan Ehrlich - Technische Universität DresdenIrina Filippi - Université Paris CitéTian Ge - Broad InstituteSudheer Giddaluru - University of BergenAaron L Goldman - Lieber Institute for Brain DevelopmentRebecca F Gottesman - Johns Hopkins UniversityCorina U Greven - Medical Research CouncilOliver Grimm - Heidelberg UniversityMichael E Griswold - University of MississippiTulio Guadalupe - Radboud University NijmegenJohanna Hass - Technische Universität DresdenUnn K Haukvik - University of OsloSaima Hilal - National University of SingaporeEdith Hofer - Medical University of GrazDavid Hoehn - Max Planck SocietyAvram J. Holmes - Yale UniversityMartine Hoogman - Radboud University NijmegenDeborah Janowitz - Universität GreifswaldTianye Jia - King's College LondonDalia Kasperaviciute - Epilepsy SocietySungeun Kim - Indiana UniversityMarieke Klein - Radboud University NijmegenBernd Kraemer - Heidelberg UniversityPhil H Lee - Broad InstituteLi LiaoDavid C Liewald - University of EdinburghLorna M Lopez - University of EdinburghMichelle Luciano - University of EdinburghChristine Macare - King's College LondonMar MarquandMar Matarin - University College LondonKaren A Mather - UNSW SydneyManuel Mattheisen - Lundbeck (United States)Bernard Mazoyer - Université de BordeauxDavid McKay - Yale UniversityRebekah McWhirter - University of TasmaniaYuri Milaneschi - Vrije Universiteit AmsterdamNazanin Mirza-Schreiber - Max Planck SocietyRyan L Muetzel - Erasmus University RotterdamSusana Muñoz Maniega - University of EdinburghKwangsik Nho - Indiana UniversityAllison C Nugent - National Institutes of HealthLoes M Olde Loohuis - University of California, Los AngelesJaap Oosterlaan - Vrije Universiteit AmsterdamMartina MartinIrene Pappa - Erasmus University RotterdamLukas Pirpamer - Medical University of GrazSara Pudas - Umeå UniversityBenno Pütz - Max Planck SocietyKumar B Rajan - Rush University Medical CenterAdaikalavan Ramasamy - University of OxfordJennifer S Richards - Radboud University NijmegenShannon L Risacher - Indiana UniversityRobert Roiz-Santiañez - Centro de Investigación Biomédica en RedNanda Rommelse - Radboud University NijmegenEmma Rose - Trinity College DublinNatalie A Royle - University of EdinburghTatjana Rundek - University of MiamiPhilipp G Sämann - Max Planck SocietyClaudia L Satizabal - Boston UniversityEPIGEN
- Contributors
- Beng Choon Ho (Contributor) - University of Iowa, Psychiatry
- Resource Type
- Journal article
- Publication Details
- Nature neuroscience, Vol.19(12), pp.1569–1582-1582
- DOI
- 10.1038/nn.4398
- PMID
- 27694991
- PMCID
- PMC5227112
- NLM abbreviation
- Nat Neurosci
- ISSN
- 1097-6256
- eISSN
- 1546-1726
- Publisher
- Nature Publishing Group
- Language
- English
- Date published
- 12/2016
- Academic Unit
- Psychiatry
- Record Identifier
- 9984280837502771
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