Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index
Open accessAbstract
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.
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Of the 15 child body mass index variants, 12 overlapped with known adult body mass index variants, illustrating the difficulty of distinguishing child and adult body mass index effects.
“From the original GWAS, 12 of the 15 child BMI overlapped with known adult BMI variants, 14 which illustrates the difficulty of distinguishing these two.”
From Commentary: Two-sample Mendelian randomization: opportunities and challenges (2016) · cites this paper as [14]
For birthweight and child body mass index, there seemed to have been no attempt to explore sex differences in the original GWAS, likely reflecting low power.
“For birthweight and child BMI, there seemed to have been no attempt to explore sex differences, which likely reflects the low power in those studies to do that.”
From Commentary: Two-sample Mendelian randomization: opportunities and challenges (2016) · cites this paper as [14]
From the original papers, the instrument for adult body mass index is stronger than for the other traits (R2 for adult body mass index, birthweight, child body mass index and waist-hip ratio are 0.027, 0.008, 0.020 and 0.013, respectively).
“From the original papers it can be seen that the instrument for adult BMI is stronger than for the other traits (the respective R 2 for adult BMI, birthweight, child BMI and WHR, are: 0.027, 0.008, 0.020 and 0.013;”
From Commentary: Two-sample Mendelian randomization: opportunities and challenges (2016) · cites this paper as [14]
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- Authors
- Felix, J. F., Bradfield, J. P., Monnereau, C., van der Valk, R. J. P., Stergiakouli, E., Chesi, A., Gaillard, R., Feenstra, B., Thiering, E., Kreiner-Møller, E., Mahajan, A., Pitkänen, N., Joro, R., Cavadino, A., Huikari, V., Franks, S., Groen-Blokhuis, M. M., Cousminer, D. L., Marsh, J. A., Lehtimäki, T., Curtin, J. A., Vioque, J., Ahluwalia, T. S., Myhre, R., Price, T. S., Vilor-Tejedor, N., Yengo, L., Grarup, N., Ntalla, I., Ang, W., Atalay, M., Bisgaard, H., Blakemore, A. I., Bonnefond, A., Carstensen, L., (BMDCS), B. M. D. I. C. S., Early Genetics and Lifecourse Epidemiology (EAGLE) consortium, Eriksson, J., Flexeder, C., Franke, L., Geller, F., Geserick, M., Hartikainen, A.-L., Haworth, C. M. A., Hirschhorn, J. N., Hofman, A., Holm, J.-C., Horikoshi, M., Hottenga, J. J., Huang, J., Kadarmideen, H. N., Kähönen, M., Kiess, W., Lakka, H.-M., Lakka, T. A., Lewin, A. M., Liang, L., Lyytikäinen, L.-P., Ma, B., Magnus, P., McCormack, S. E., McMahon, G., Mentch, F. D., Middeldorp, C. M., Murray, C. S., Pahkala, K., Pers, T. H., Pfäffle, R., Postma, D. S., Power, C., Simpson, A., Sengpiel, V., Tiesler, C. M. T., Torrent, M., Uitterlinden, A. G., van Meurs, J. B., Vinding, R., Waage, J., Wardle, J., Zeggini, E., Zemel, B. S., Dedoussis, G. V., Pedersen, O., Froguel, P., Sunyer, J., Plomin, R., Jacobsson, B., Hansen, T., Gonzalez, J. R., Custovic, A., Raitakari, O. T., Pennell, C. E., Widén, E., Boomsma, D. I., Koppelman, G. H., Sebert, S., Järvelin, M.-R., Hyppönen, E., McCarthy, M. I., Lindi, V., Harri, N., Körner, A., Bønnelykke, K., Heinrich, J., Melbye, M., Rivadeneira, F., Hakonarson, H., Ring, S. M., Smith, G. D., Sørensen, T. I. A., Timpson, N. J., Grant, S. F. A., & Jaddoe, V. W. V.
- Affiliations
- Erasmus MC (NL)
- Centre for Applied Genomics (CA)
- University of Bristol (GB)
- Statens Serum Institut (DK)
- Helmholtz Munich (DE)
- Centre for Human Genetics (GB)
- University of Eastern Finland (FI)
- Queen Mary University of London (GB)
- University of Helsinki (FI)
- The University of Western Australia (AU)
- Fimlab (Finland) (FI)
- Manchester Academic Health Science Centre (GB)
- University of Copenhagen (DK)
- University of Pennsylvania (US)
- Centre National de la Recherche Scientifique (FR)
- Gentofte Hospital (DK)
- Imperial College London (GB)
- Finnish Institute for Health and Welfare (FI)
- University of Warwick (GB)
- Broad Institute (US)
- Shanghai Jiao Tong University (CN)
- Tampere University Hospital (FI)
- Harvard University (US)
- Norwegian Institute of Public Health (NO)
- Amsterdam Neuroscience (NL)
- Leipzig University (DE)
- University College London (GB)
- University of Manchester (GB)
- Sahlgrenska University Hospital (SE)
- Wellcome Sanger Institute (GB)
- Children's Hospital of Philadelphia (US)
- Universitat Pompeu Fabra (ES)
- King's College London (GB)
- University Medical Center Groningen (NL)
- Oulu University Hospital (FI)
- University of South Australia (AU)
- University of Turku (FI)
- Corresponding author
- Felix, Janine F.
- ORCID
- Felix, Janine F.
- Monnereau, Claire
- Stergiakouli, Evie
- Chesi, Alessandra
- Gaillard, Romy
- Feenstra, Bjarke
- Thiering, Elisabeth
- Mahajan, Anubha
- Pitkänen, Niina
- Cavadino, Alana
- Marsh, Julie A.
- Lehtimäki, Terho
- Curtin, John A.
- Ahluwalia, Tarunveer S.
- Myhre, Ronny
- Price, Thomas S.
- Yengo, Loïc
- Grarup, Niels
- Atalay, Mustafa
- Bisgaard, Hans
- Blakemore, Alexandra I.
- Carstensen, Lisbeth
- Eriksson, Johan
- Flexeder, Claudia
- Franke, Lude
- Geller, Frank
- Haworth, Claire M.A.
- Hirschhorn, Joel N.
- Holm, Jens-Christian
- Horikoshi, Momoko
- Hottenga, Jouke Jan
- Huang, Jinyan
- Kadarmideen, Haja N.
- Kähönen, Mika
- Kiess, Wieland
- Lakka, Timo A.
- Liang, Liming
- Lyytikäinen, Leo-Pekka
- Ma, Baoshan
- Magnus, Per
- McCormack, Shana E.
- Mentch, Frank D.
- Middeldorp, Christel M.
- Murray, Clare S.
- Pahkala, Katja
- Pers, Tune H.
- Pfäffle, Roland
- Postma, Dirkje S.
- Power, Christine
- Simpson, Angela
- Sengpiel, Verena
- Uitterlinden, André G.
- Vinding, Rebecca
- Waage, Johannes
- Wardle, Jane
- Zeggini, Eleftheria
- Zemel, Babette S.
- Dedoussis, George V.
- Pedersen, Oluf
- Froguel, Philippe
- Sunyer, Jordi
- Plomin, Robert
- Jacobsson, Bo
- Hansen, Torben
- Raitakari, Olli T.
- Pennell, Craig E.
- Widén, Elisabeth
- Boomsma, Dorret I.
- Koppelman, Gerard H.
- Sebert, Sylvain
- Järvelin, Marjo-Riitta
- Hyppönen, Elina
- McCarthy, Mark I.
- Lindi, Virpi
- Körner, Antje
- Bønnelykke, Klaus
- Heinrich, Joachim
- Melbye, Mads
- Rivadeneira, Fernando
- Hakonarson, Hakon
- Ring, Susan M.
- Smith, George Davey
- Sørensen, Thorkild I.A.
- Timpson, Nicholas J.
- Grant, Struan F.A.
- Jaddoe, Vincent W.V.
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-11-24
- Volume
- 25
- Issue
- 2
- Pages
- 389-403
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- PMC
- PMC4854022
- OpenAlex
- W2216513861
- Cited by
- 343
- References
- 46
- Citations by year
- 2026: 10 · 2025: 20 · 2024: 30 · 2023: 32 · 2022: 37 · 2021: 36 · 2020: 45 · 2019: 36 · 2018: 41 · 2017: 37 · 2016: 17
- FWCI
- 21.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Human Molecular Genetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- UWA Profiles and Research Repository (UWA) (publishedVersion, other-oa)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, other-oa)
- VU Research Portal (publishedVersion, other-oa)
- Research Portal (King's College London) (submittedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Site cant be reached (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
- Bristol Research (University of Bristol) (submittedVersion)
- STM:n Hallinnonalan avoin julkaisuarkisto (Julkari) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- Juvenile Diabetes Research Foundation International
- Strategiske Forskningsråd
- Itä-Suomen Yliopisto
- Fundació la Marató de TV3
- Wellcome Trust (085475/Z/08/Z, 068545/Z/02), 102215/2/13/2), 090367, 098381, 102215, 202802/Z/16/Z, 068545, 085475/B/08/Z, 098051, 076113)
- Georgia Clinical and Translational Science Alliance
- Cancer Research UK (14133)
- National Institute for Health and Care Research (NF-SI-0611-10099)
- Diabetes UK
- Asthma and Lung UK
- University of Oxford
- European Commission (279153)
- University of Bristol
- Deutsche Forschungsgemeinschaft
- ZonMw
- Erasmus Universiteit Rotterdam
- Kela
- Bundesministerium für Bildung und Forschung
- Generalitat de Catalunya
- Erasmus Medisch Centrum
- Suomen Kulttuurirahasto
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (14192, 480-04-004)
- Generalitat Valenciana
- Lundbeckfonden (R163-2013-16235, R190 2014-3904)
- Juho Vainion Säätiö
- Kuopion Yliopistollinen Sairaala
- Novo Nordisk
- Helmholtz-Zentrum für Umweltforschung
- Ministerio de Ciencia e Innovación
- Norges Forskningsråd
- Oulun Yliopisto
- Svenska Läkaresällskapet
- Paavo Nurmen Säätiö
- Universität Leipzig
- Lung Foundation Netherlands
- National Institutes of Health (5u01hg004423-02, 6r01hl087679-03, UL1TR001425, n01es75558-11-0-1, 5rl1mh083268-05, UL1TR000077)
- Canadian Institutes of Health Research (MOP82893)
- Medical Research Council (MR/N01104X/1, MR/K002449/1, MR/M013138/1, MR/M012638/1, MR/K002449/2, MC_PC_15018)
- Engineering and Physical Sciences Research Council
- Biotechnology and Biological Sciences Research Council
- Instituto de Salud Carlos III
- NIHR Imperial Biomedical Research Centre
- Münchner Zentrum für Gesundheitswissenschaften, Ludwig-Maximilians-Universität München
- Biocenter, University of Oulu
- National Heart, Lung, and Blood Institute (5R01 HL087679-02, R01 HL087679)
- National Institute of Mental Health (R01MH063706, RL1-MH083268, 1RL1MH083268-01, 5R01 MH63706:02)
- National Human Genome Research Institute (U01-HG004423, U01HG004446, U01HG004438)
- National Cancer Institute (R01CA166945)
- National Institute of Allergy and Infectious Diseases
- National Institute of Diabetes and Digestive and Kidney Diseases (K23DK102659, K12DK094723, U01DK062418, P30DK098722, R01DK075787)
- National Institute of Neurological Disorders and Stroke (2UO1 NS047537-06A1, U01NS047537, 1 UO1 NS 047537‐01)
- National Institute of Environmental Health Sciences (N01 ES075558, P30ES013508)
- National Institute of Child Health and Human Development
- National Center for Advancing Translational Sciences
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD056465, R01HD058886, R01 HD58886, R01HD076321)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Nutrition, Genetics, and Disease
- Keywords
- childhood body mass index, obesity genetics, genetic susceptibility loci, novel genetic loci, Elp3, Rab27b, ADAM23, polygenic risk score, FTO, melanocortin-4 receptor, TFAP2B
- MeSH terms
- Adolescent, Adult, Child, Child, Preschool, Female, Humans, Male, Obesity, Risk, Body Mass Index, Polymorphism, Single Nucleotide, White People, Genome-Wide Association Study, Young Adult, Genetic Loci
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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