title: Population genetic differentiation of height and body mass index across Europe.
abstract: Across-nation differences in the mean values for complex traits are common, but the reasons for these differences are unknown. Here we find that many independent loci contribute to population genetic differences in height and body mass index (BMI) in 9,416 individuals across 14 European countries. Using discovery data on over 250,000 individuals and unbiased effect size estimates from 17,500 sibling pairs, we estimate that 24% (95% credible interval (CI) = 9%, 41%) and 8% (95% CI = 4%, 16%) of the captured additive genetic variance for height and BMI, respectively, reflect population genetic differences. Population genetic divergence differed significantly from that in a null model (height, P < 3.94 × 10(-8); BMI, P < 5.95 × 10(-4)), and we find an among-population genetic correlation for tall and slender individuals (r = -0.80, 95% CI = -0.95, -0.60), consistent with correlated selection for both phenotypes. Observed differences in height among populations reflected the predicted genetic means (r = 0.51; P < 0.001), but environmental differences across Europe masked genetic differentiation for BMI (P < 0.58).
authors.affiliation: Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Robinson
authors.affiliation: Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Gibran
authors.initials: G
authors.lastname: Hemani
authors.affiliation: Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Carolina
authors.initials: C
authors.lastname: Medina-Gomez
authors.affiliation: Institute for Maternal and Child Health, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) 'Burlo Garofolo', Trieste, Italy.|Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
authors.forename: Massimo
authors.initials: M
authors.lastname: Mezzavilla
authors.affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia.|Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts, USA.|Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.|Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Tonu
authors.initials: T
authors.lastname: Esko
authors.affiliation: Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Shakhbazov
authors.affiliation: Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.|University of Queensland Diamantina Institute, University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Powell
authors.affiliation: Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Anna
authors.initials: A
authors.lastname: Vinkhuyzen
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Sonja I
authors.initials: SI
authors.lastname: Berndt
authors.affiliation: Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Stefan
authors.initials: S
authors.lastname: Gustafsson
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Anne E
authors.initials: AE
authors.lastname: Justice
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.|Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Bratati
authors.initials: B
authors.lastname: Kahali
authors.affiliation: Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Adam E
authors.initials: AE
authors.lastname: Locke
authors.affiliation: Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts, USA.|Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.|Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.|Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.
authors.forename: Tune H
authors.initials: TH
authors.lastname: Pers
authors.affiliation: Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts, USA.|Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Sailaja
authors.initials: S
authors.lastname: Vedantam
authors.affiliation: Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, UK.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Wood
authors.affiliation: Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Wouter
authors.initials: W
authors.lastname: van Rheenen
authors.affiliation: Norwegian Centre for Mental Disorders Research (NORMENT), KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Ole A
authors.initials: OA
authors.lastname: Andreassen
authors.affiliation: Institute for Maternal and Child Health, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) 'Burlo Garofolo', Trieste, Italy.|Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
authors.forename: Paolo
authors.initials: P
authors.lastname: Gasparini
authors.affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia.
authors.forename: Andres
authors.initials: A
authors.lastname: Metspalu
authors.affiliation: Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Leonard H van den
authors.initials: LH
authors.lastname: Berg
authors.affiliation: Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Jan H
authors.initials: JH
authors.lastname: Veldink
authors.affiliation: Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Fernando
authors.initials: F
authors.lastname: Rivadeneira
authors.affiliation: Institute of Biological Psychiatry, MHC Sct. Hans, Mental Health Devices Copenhagen, Roskilde, Denmark.|Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.|Lundbeck Foundation Initiative for Integrative Psychiatric Research, (iPSYCH), Aarhus, Denmark.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Werge
authors.affiliation: Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Goncalo R
authors.initials: GR
authors.lastname: Abecasis
authors.affiliation: Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.|EMGO+ Institute for Health and Care Research, VU University Medical Center, Amsterdam, the Netherlands.|Department of Biological Psychology, VU University Amsterdam, Amsterdam, the Netherlands.
authors.forename: Dorret I
authors.initials: DI
authors.lastname: Boomsma
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.|Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Chasman
authors.affiliation: Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.|EMGO+ Institute for Health and Care Research, VU University Medical Center, Amsterdam, the Netherlands.|Department of Biological Psychology, VU University Amsterdam, Amsterdam, the Netherlands.
authors.forename: Eco J C
authors.initials: EJ
authors.lastname: de Geus
authors.affiliation: Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, UK.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Frayling
authors.affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia.|Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts, USA.|Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.|Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Joel N
authors.initials: JN
authors.lastname: Hirschhorn
authors.affiliation: Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.|EMGO+ Institute for Health and Care Research, VU University Medical Center, Amsterdam, the Netherlands.|Department of Biological Psychology, VU University Amsterdam, Amsterdam, the Netherlands.
authors.forename: Jouke Jan
authors.initials: JJ
authors.lastname: Hottenga
authors.affiliation: Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.|Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
authors.forename: Erik
authors.initials: E
authors.lastname: Ingelsson
authors.affiliation: Medical Research Council (MRC) Epidemiology Unit, University of Cambridge, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.|Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Genetics of Obesity and Related Metabolic Traits Program, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Ruth J F
authors.initials: RJ
authors.lastname: Loos
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Patrik K E
authors.initials: PK
authors.lastname: Magnusson
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Martin
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Grant W
authors.initials: GW
authors.lastname: Montgomery
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.|Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA.|Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Kari E
authors.initials: KE
authors.lastname: North
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Pedersen
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London, St. Thomas' Hospital, London, UK.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Spector
authors.affiliation: Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Elizabeth K
authors.initials: EK
authors.lastname: Speliotes
authors.affiliation: Biosciences Research Division, Department of Primary Industries, Melbourne, Victoria, Australia.|Department of Food and Agricultural Systems, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Goddard
authors.affiliation: Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.|University of Queensland Diamantina Institute, University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia.
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.affiliation: Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.|University of Queensland Diamantina Institute, University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia.
authors.forename: Peter M
authors.identifier: http://orcid.org/0000-0002-2143-8760
authors.initials: PM
authors.lastname: Visscher
mesh_terms: D000465:Algorithms; D001827:Body Height / Q000235:genetics*; D015992:Body Mass Index; D005060:Europe; D020869:Gene Expression Profiling / Q000379:methods / Q000706:statistics & numerical data; D059647:Gene-Environment Interaction; D014644:Genetic Variation; D005828:Genetics, Population / Q000379:methods / Q000706:statistics & numerical data*; D055106:Genome-Wide Association Study / Q000379:methods / Q000706:statistics & numerical data; D005838:Genotype; D005843:Geography; D006801:Humans; D008957:Models, Genetic; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D025341:Principal Component Analysis