Format

Send to

Choose Destination
Hum Mol Genet. 2016 Jan 15;25(2):389-403. doi: 10.1093/hmg/ddv472. Epub 2015 Nov 24.

Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index.

Felix JF1, Bradfield JP2, Monnereau C3, van der Valk RJ4, Stergiakouli E5, Chesi A6, Gaillard R3, Feenstra B7, Thiering E8, Kreiner-Møller E9, Mahajan A10, Pitkänen N11, Joro R12, Cavadino A13, Huikari V14, Franks S15, Groen-Blokhuis MM16, Cousminer DL17, Marsh JA18, Lehtimäki T19, Curtin JA20, Vioque J21, Ahluwalia TS22, Myhre R23, Price TS24, Vilor-Tejedor N25, Yengo L26, Grarup N27, Ntalla I28, Ang W18, Atalay M12, Bisgaard H9, Blakemore AI29, Bonnefond A26, Carstensen L7; Bone Mineral Density in Childhood Study (BMDCS); Early Genetics and Lifecourse Epidemiology (EAGLE) consortium, Eriksson J30, Flexeder C31, Franke L32, Geller F7, Geserick M33, Hartikainen AL34, Haworth CM35, Hirschhorn JN36, Hofman A37, Holm JC38, Horikoshi M39, Hottenga JJ16, Huang J40, Kadarmideen HN41, Kähönen M42, Kiess W43, Lakka HM12, Lakka TA44, Lewin AM45, Liang L46, Lyytikäinen LP19, Ma B47, Magnus P48, McCormack SE49, McMahon G5, Mentch FD2, Middeldorp CM16, Murray CS20, Pahkala K50, Pers TH51, Pfäffle R52, Postma DS4, Power C53, Simpson A54, Sengpiel V55, Tiesler CM8, Torrent M56, Uitterlinden AG57, van Meurs JB58, Vinding R59, Waage J9, Wardle J60, Zeggini E61, Zemel BS62, Dedoussis GV63, Pedersen O27, Froguel P64, Sunyer J65, Plomin R66, Jacobsson B67, Hansen T27, Gonzalez JR25, Custovic A20, Raitakari OT68, Pennell CE18, Widén E17, Boomsma DI16, Koppelman GH69, Sebert S70, Järvelin MR71, Hyppönen E72, McCarthy MI73, Lindi V12, Harri N74, Körner A43, Bønnelykke K9, Heinrich J31, Melbye M75, Rivadeneira F57, Hakonarson H76, Ring SM77, Smith GD5, Sørensen TI78, Timpson NJ5, Grant SF79, Jaddoe VW3; Early Growth Genetics (EGG) Consortium; Bone Mineral Density in Childhood Study BMDCS.

Author information

1
The Generation R Study Group, Department of Pediatrics, Department of Epidemiology, j.felix@erasmusmc.nl.
2
Center for Applied Genomics.
3
The Generation R Study Group, Department of Pediatrics, Department of Epidemiology.
4
Department of Pulmonology, GRIAC (Groningen Research Institute for Asthma and COPD).
5
MRC Integrative Epidemiology Unit at the University of Bristol.
6
Division of Human Genetics.
7
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
8
Institute of Epidemiology I, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany, Division of Metabolic and Nutritional Medicine, Dr von Hauner Children's Hospital, University of Munich Medical Center, Munich, Germany.
9
COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital.
10
Wellcome Trust Centre for Human Genetics.
11
Research Centre of Applied and Preventive Cardiovascular Medicine, Institute of Clinical Medicine, Neurology.
12
Institute of Biomedicine, Physiology, University of Eastern Finland, Kuopio, Finland.
13
Centre for Environmental and Preventive Medicine, Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, UK, Population, Policy and Practice, UCL Institute of Child Health.
14
Centre for Life Course Epidemiology.
15
Institute of Reproductive and Developmental Biology.
16
Department of Biological Psychology, VU University Amsterdam, NCA Neuroscience Campus Amsterdam, EMGO+ Institute for Health and Care Research, Amsterdam, the Netherlands.
17
Institute for Molecular Medicine, Finland (FIMM), University of Helsinki, Helsinki, Finland.
18
School of Women's and Infants' Health, The University of Western Australia, Perth, Australia.
19
Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland, Department of Clinical Chemistry.
20
Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, University of Manchester and University Hospital of South Manchester, Manchester Academic Health Sciences Centre, Manchester, UK.
21
Universidad Miguel Hernandez, Elche-Alicante, Spain, CIBER Epidemiología y Salud Pública (CIBERESP), Spain.
22
COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, Novo Nordisk Foundation Centre for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark, Steno Diabetes Center, Gentofte, Denmark.
23
Department of Genes and Envrionment, Division of Epidemiology.
24
Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine, USA.
25
CIBER Epidemiología y Salud Pública (CIBERESP), Spain, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain, Pompeu Fabra University (UPF), Barcelona, Spain.
26
CNRS UMR8199, Pasteur Institute Lille, France, European Genomic Institute for Diabetes (EGID), Lille, France.
27
Novo Nordisk Foundation Centre for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
28
Department of Health Sciences, University of Leicester, Leicester, UK, Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece.
29
Section of Investigative Medicine, Division of Diabetes, Endocrinology, and Metabolism, Faculty of Medicine, Imperial College, London, UK.
30
National Institute for Health and Welfare, Helsinki, Finland.
31
Institute of Epidemiology I, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
32
Department of Genetics.
33
Center of Pediatric Research, Department of Women's and Child Health, LIFE Child (Leipzig Research Center for Civilization Diseases).
34
Institute of Clinical Medicine/Obstetrics and Gynecology.
35
Department of Psychology, University of Warwick, UK.
36
Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, USA, Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, USA, Department of Genetics, Harvard Medical School, Boston, USA.
37
The Generation R Study Group, Department of Epidemiology.
38
The Children's Obesity Clinic, Department of Pediatrics, Copenhagen University Hospital Holbæk, The Danish Childhood Obesity Biobank, Denmark, Institute of Medicine, Copenhagen University, Copenhagen, Denmark.
39
Wellcome Trust Centre for Human Genetics, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
40
State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China.
41
Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark.
42
Department of Clinical Physiology, University of Tampere School of Medicine, Tampere, Finland, Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland.
43
Center of Pediatric Research, Department of Women's and Child Health.
44
Institute of Biomedicine, Physiology, University of Eastern Finland, Kuopio, Finland, Kuopio Research Institute of Exercise Medicine, Kuopio, Finland, Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland.
45
Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPE) Centre for Environment and Health, School of Public Health, Imperial College London, UK.
46
Department of Epidemiology, Department of Biostatistics, Harvard School of Public Health, Boston, USA.
47
College of Information Science and Technology, Dalian Maritime University, Dalian, Liaoning Province, China.
48
Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway.
49
Division of Human Genetics, Division of Endocrinology, Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
50
Research Centre of Applied and Preventive Cardiovascular Medicine, Department of Health and Physical Activity, Paavo Nurmi Centre, Sports and Exercise Medicine Unit.
51
Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, USA, Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, USA.
52
Center of Pediatric Research, Department of Women's and Child Health, CrescNet, Medical Faculty, University of Leipzig, Germany.
53
Population, Policy and Practice, UCL Institute of Child Health.
54
Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, University of Manchester and.
55
Department of Obstetrics and Gynecology, Sahlgrenska Academy, Sahlgrenska University Hosptial, Gothenburg, Sweden.
56
CIBER Epidemiología y Salud Pública (CIBERESP), Spain, Area de Salut de Menorca, ib-salut, Menorca, Spain.
57
The Generation R Study Group, Department of Epidemiology, Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
58
Department of Epidemiology, Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
59
Department of Pediatrics, Naestved Hospital, Naestved, Denmark, COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital.
60
Department of Epidemiology and Public Health, University College London, UK.
61
Wellcome Trust Sanger Institute, The Morgan Building, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, UK.
62
Division of Gastroenterology, Hepatology and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, PA, USA, Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
63
Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece.
64
CNRS UMR8199, Pasteur Institute Lille, France, Department of Genomics of Common Disease, School of Public Health, Imperial College London, Hammersmith Hospital, London, UK.
65
CIBER Epidemiología y Salud Pública (CIBERESP), Spain, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain, Pompeu Fabra University (UPF), Barcelona, Spain, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
66
King's College London, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, De Crespigny Park, London, UK.
67
Department of Genes and Envrionment, Division of Epidemiology, Department of Obstetrics and Gynecology, Sahlgrenska Academy, Sahlgrenska University Hosptial, Gothenburg, Sweden.
68
Research Centre of Applied and Preventive Cardiovascular Medicine, Department of Clinical Physiology and Nuclear Medicine.
69
Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, GRIAC (Groningen Research Institute for Asthma and COPD), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
70
Centre for Life Course Epidemiology, Biocenter Oulu, University of Oulu, Oulu, Finland.
71
Centre for Life Course Epidemiology, Biocenter Oulu, University of Oulu, Oulu, Finland, Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPE) Centre for Environment and Health, School of Public Health, Imperial College London, UK, Unit of Primary Care, Oulu University Hospital, Oulu, Finland, Department of Children and Young People and Families, National Institute for Health and Welfare, Oulu, Finland.
72
Population, Policy and Practice, UCL Institute of Child Health, School of Population Health and Sansom Institute, University of South Australia, Adelaide, Australia, South Australian Health and Medical Research Institute, Adelaide, Australia.
73
Wellcome Trust Centre for Human Genetics, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK, Oxford National Institute for Health Research (NIHR) Biomedical Research Centre, Churchill Hospital, Oxford, UK.
74
Department of Pediatrics, Turku University Hospital, University of Turku, Turku, Finland.
75
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA and.
76
Center for Applied Genomics, Division of Human Genetics, Department of Obstetrics and Gynecology, Sahlgrenska Academy, Sahlgrenska University Hosptial, Gothenburg, Sweden.
77
MRC Integrative Epidemiology Unit at the University of Bristol, Avon Longitudinal Study of Parents and Children (ALSPAC), School of Social and Community Medicine, University of Bristol, Bristol, UK.
78
MRC Integrative Epidemiology Unit at the University of Bristol, Novo Nordisk Foundation Centre for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark, Institute of Preventive Medicine, Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark.
79
Center for Applied Genomics, Division of Human Genetics, Division of Endocrinology, Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Abstract

A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown. We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation scores. We included 35 668 children from 20 studies in the discovery phase and 11 873 children from 13 studies in the replication phase. In total, 15 loci reached genome-wide significance (P-value < 5 × 10(-8)) in the joint discovery and replication analysis, of which 12 are previously identified loci in or close to ADCY3, GNPDA2, TMEM18, SEC16B, FAIM2, FTO, TFAP2B, TNNI3K, MC4R, GPR61, LMX1B and OLFM4 associated with adult body mass index or childhood obesity. We identified three novel loci: rs13253111 near ELP3, rs8092503 near RAB27B and rs13387838 near ADAM23. Per additional risk allele, body mass index increased 0.04 Standard Deviation Score (SDS) [Standard Error (SE) 0.007], 0.05 SDS (SE 0.008) and 0.14 SDS (SE 0.025), for rs13253111, rs8092503 and rs13387838, respectively. A genetic risk score combining all 15 SNPs showed that each additional average risk allele was associated with a 0.073 SDS (SE 0.011, P-value = 3.12 × 10(-10)) increase in childhood body mass index in a population of 1955 children. This risk score explained 2% of the variance in childhood body mass index. This study highlights the shared genetic background between childhood and adult body mass index and adds three novel loci. These loci likely represent age-related differences in strength of the associations with body mass index.

PMID:
26604143
PMCID:
PMC4854022
DOI:
10.1093/hmg/ddv472
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Grant support

Publication types

MeSH terms

Grant support

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center