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Nat Genet. 2015 Nov;47(11):1357-62. doi: 10.1038/ng.3401. Epub 2015 Sep 14.

Population genetic differentiation of height and body mass index across Europe.

Author information

1
Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.
2
Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
3
Institute for Maternal and Child Health, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) 'Burlo Garofolo', Trieste, Italy.
4
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
5
Estonian Genome Center, University of Tartu, Tartu, Estonia.
6
Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts, USA.
7
Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
8
Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
9
University of Queensland Diamantina Institute, University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia.
10
Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA.
11
Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
12
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
13
Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
14
Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA.
15
Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.
16
Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.
17
Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, UK.
18
Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
19
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.
20
Institute of Biological Psychiatry, MHC Sct. Hans, Mental Health Devices Copenhagen, Roskilde, Denmark.
21
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
22
Lundbeck Foundation Initiative for Integrative Psychiatric Research, (iPSYCH), Aarhus, Denmark.
23
Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
24
EMGO+ Institute for Health and Care Research, VU University Medical Center, Amsterdam, the Netherlands.
25
Department of Biological Psychology, VU University Amsterdam, Amsterdam, the Netherlands.
26
Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
27
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
28
Medical Research Council (MRC) Epidemiology Unit, University of Cambridge, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.
29
Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
30
Genetics of Obesity and Related Metabolic Traits Program, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
31
Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
32
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
33
QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
34
Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
35
Department of Twin Research and Genetic Epidemiology, King's College London, St. Thomas' Hospital, London, UK.
36
Biosciences Research Division, Department of Primary Industries, Melbourne, Victoria, Australia.
37
Department of Food and Agricultural Systems, University of Melbourne, Melbourne, Victoria, Australia.

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).

PMID:
26366552
PMCID:
PMC4984852
DOI:
10.1038/ng.3401
[Indexed for MEDLINE]
Free PMC Article

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