title: Common variants at 12q15 and 12q24 are associated with infant head circumference.
abstract: To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association studies (GWAS) (N = 10,768 individuals of European ancestry enrolled in pregnancy and/or birth cohorts) and followed up three lead signals in six replication studies (combined N = 19,089). rs7980687 on chromosome 12q24 (P = 8.1 × 10(-9)) and rs1042725 on chromosome 12q15 (P = 2.8 × 10(-10)) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height, their effects on infant head circumference were largely independent of height (P = 3.8 × 10(-7) for rs7980687 and P = 1.3 × 10(-7) for rs1042725 after adjustment for infant height). A third signal, rs11655470 on chromosome 17q21, showed suggestive evidence of association with head circumference (P = 3.9 × 10(-6)). SNPs correlated to the 17q21 signal have shown genome-wide association with adult intracranial volume, Parkinson's disease and other neurodegenerative diseases, indicating that a common genetic variant in this region might link early brain growth with neurological disease in later life.
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.|Department of Paediatrics, Erasmus Medical Center, Rotterdam, The Netherlands.|The Generation R Study Group, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: H Rob
authors.initials: HR
authors.lastname: Taal
authors.affiliation: MRC Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Beate St
authors.initials: BS
authors.lastname: Pourcain
authors.affiliation: Institute of Epidemiology I, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Thiering
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, UK.
authors.forename: Shikta
authors.initials: S
authors.lastname: Das
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.|Department of Paediatrics, Erasmus Medical Center, Rotterdam, The Netherlands.|The Generation R Study Group, Erasmus Medical Center, Rotterdam, The Netherlands.|Weill Cornell Medical College - Qatar, Doha, Qatar.
authors.forename: Dennis O
authors.initials: DO
authors.lastname: Mook-Kanamori
authors.affiliation: School of Women's and Infants' Health, The University of Western Australia, Perth, Australia.|Samuel Lunenfeld Research Institute, University of Toronto, Toronto, Canada.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Warrington
authors.affiliation: Institute of Health Sciences, University of Oulu, Finland.|Biocenter Oulu, University of Oulu, Finland.
authors.forename: Marika
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authors.lastname: Kaakinen
authors.affiliation: Copenhagen Prospective Studies on Asthma in Childhood, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Eskil
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authors.lastname: Kreiner-Møller
authors.affiliation: Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
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authors.lastname: Bradfield
authors.affiliation: Genetics of Complex Traits, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter, UK.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Freathy
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Frank
authors.initials: F
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authors.affiliation: Center for Research in Environmental Epidemiology (CREAL), Barcelona, Catalonia, Spain.|Hospital del Mar Research Institute (IMIM), Barcelona, Catalonia, Spain.|CIBER Epidemiologia y Salud Pública (CIBERESP), Barcelona, Catalonia, Spain.
authors.forename: Mònica
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authors.lastname: Guxens
authors.affiliation: Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
authors.forename: Diana L
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authors.affiliation: Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
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authors.affiliation: MRC Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Timpson
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.|Department of Radiology, Erasmus Medical Center, Rotterdam, The Netherlands.
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authors.initials: MA
authors.lastname: Ikram
authors.affiliation: School of Medicine and Pharmacology, The University of Western Australia, Perth, Australia.
authors.forename: Lawrence J
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authors.affiliation: Copenhagen Prospective Studies on Asthma in Childhood, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Klaus
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authors.affiliation: Department of Genomics of Common Disease, School of Public Health, Imperial College London.
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authors.initials: JL
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authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, UK.|Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
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authors.affiliation: Copenhagen Prospective Studies on Asthma in Childhood, University of Copenhagen, Copenhagen, Denmark.
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authors.initials: BLK
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authors.affiliation: National Institute for Health and Welfare, Helsinki, Finland.|Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland.|Folkhalsan Research Centre, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
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authors.affiliation: MRC Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Bristol, UK.
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authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.|The Generation R Study Group, Erasmus Medical Center, Rotterdam, The Netherlands.
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authors.initials: A
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authors.affiliation: MRC Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Bristol, UK.
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authors.affiliation: Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
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authors.affiliation: Research Unit for Molecular Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.|Hannover Unified Biobank, Hannover Medical School, Hannover, Germany.
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authors.affiliation: Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
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authors.affiliation: Institute of Medical Informatics, Biometry and Epidemiology, Chair of Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany.|Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.|Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians-Universität, Munich, Germany.
authors.forename: Martina
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authors.affiliation: Department of Epidemiology and Biostatistics, Imperial College London, W2 1PG London, UK.
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authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK.|Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
authors.forename: Inga
authors.initials: I
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authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.|Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
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authors.affiliation: Department of Obstetrics & Gynecology, Erasmus Medical Center, Rotterdam, The Netherlands.
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authors.affiliation: Center for Research in Environmental Epidemiology (CREAL), Barcelona, Catalonia, Spain.|Hospital del Mar Research Institute (IMIM), Barcelona, Catalonia, Spain.|CIBER Epidemiologia y Salud Pública (CIBERESP), Barcelona, Catalonia, Spain.|Pompeu Fabra University (UPF), Barcelona, Catalonia, Spain.
authors.forename: Jordi
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authors.affiliation: Institute of Epidemiology I, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.|Dr Von Hauner Children's Hospital, Ludwig-Maximilians University Munich, Munich, Germany.
authors.forename: Carla
authors.initials: C
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authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
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authors.initials: MMB
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authors.affiliation: Icelandic Heart Association, Kopavogus, Iceland.|University of Iceland, Reykjavik, Iceland.
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authors.affiliation: Department of Medicine (Geriatrics), University of Mississippi Medical Center, Jackson, MS, USA.
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authors.affiliation: Icelandic Heart Association, Kopavogus, Iceland.|University of Iceland, Reykjavik, Iceland.
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authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.|Department of Radiology, Erasmus Medical Center, Rotterdam, The Netherlands.
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authors.affiliation: Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.|Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.|Department of Pediatrics, University of Pennsylvania, Philadelphia PA 19104, USA.
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authors.affiliation: CIBER Epidemiologia y Salud Pública (CIBERESP), Barcelona, Catalonia, Spain.|Division of Environment and Health, Center for Public Health Research-CSISP, Valencia, Spain.
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authors.affiliation: Centre National de Génotypage, Evry, France.|Foundation Jean Dausset, CEPH, Paris, France.
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authors.affiliation: Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.|Department of Medical Genetics, University of Helsinki, Helsinki, Finland.|Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.|Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Aarno
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authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
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authors.initials: SM
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authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, UK.|London School of Hygiene and Tropical Medicine, London, United Kingdom.
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authors.affiliation: Institute of Epidemiology I, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
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authors.initials: AG
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authors.affiliation: Institute of Epidemiology I, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.|Institute of Medical Informatics, Biometry and Epidemiology, Chair of Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany.|Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians-Universität, Munich, Germany.
authors.forename: H-Erich
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authors.affiliation: Copenhagen Prospective Studies on Asthma in Childhood, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Nadja Hawwa
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authors.affiliation: Department of Neurology and Center for Neuroscience, University of California at Davis, Sacramento, CA, USA.
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authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
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authors.initials: CM
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authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK.|Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.|Oxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford, UK.
authors.forename: Mark I
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authors.affiliation: Department of Pediatric Pulmonology and Pediatric Allergology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Gerard H
authors.initials: GH
authors.lastname: Koppelman
authors.affiliation: CIBER Epidemiologia y Salud Pública (CIBERESP), Barcelona, Catalonia, Spain.|Pompeu Fabra University (UPF), Barcelona, Catalonia, Spain.|Genes and Disease Program, Center for Genomic Regulation (CRG-UPF), Barcelona, Catalonia, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Estivill
authors.affiliation: Peninsula NIHR Clinical Research Facility, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter, UK.
authors.forename: Andrew T
authors.initials: AT
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authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
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authors.affiliation: Copenhagen Prospective Studies on Asthma in Childhood, University of Copenhagen, Copenhagen, Denmark.
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authors.affiliation: School of Women's and Infants' Health, The University of Western Australia, Perth, Australia.
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authors.initials: CE
authors.lastname: Pennell
authors.affiliation: Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Widen
authors.affiliation: Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.|Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.|Department of Pediatrics, University of Pennsylvania, Philadelphia PA 19104, USA.
authors.forename: Hakon
authors.initials: H
authors.lastname: Hakonarson
authors.affiliation: MRC Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: George Davey
authors.initials: GD
authors.lastname: Smith
authors.affiliation: Institute of Epidemiology I, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Heinrich
authors.affiliation: Institute of Health Sciences, University of Oulu, Finland.|National Institute for Health and Welfare, Oulu, Finland, Biocenter Oulu, University of Oulu, Finland.|Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, MRC Health Protection Agency (HPA) Centre for Environment and Health, Imperial College London.
authors.forename: Marjo-Riitta
authors.initials: MR
authors.lastname: Jarvelin
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.|Department of Paediatrics, Erasmus Medical Center, Rotterdam, The Netherlands.|The Generation R Study Group, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Vincent W V
authors.initials: VWV
authors.lastname: Jaddoe
mesh_terms: D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D011247:Pregnancy; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D056426:Genetic Loci; D005819:Genetic Markers; D055106:Genome-Wide Association Study; D006257:Head / Q000254:growth & development / Q000473:pathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011248:Pregnancy Complications / Q000209:etiology / Q000473:pathology; D044465:White People / Q000235:genetics
chemical_list: D005819:Genetic Markers