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Record W2216513861 · doi:10.1093/hmg/ddv472

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

2015· review· en· W2216513861 on OpenAlexfundno aff
Janine F. Felix, Jonathan P. Bradfield, Claire Monnereau, Ralf J.P. van der Valk, Evie Stergiakouli, Alessandra Chesi, Romy Gaillard, Bjarke Feenstra, Elisabeth Thiering, Eskil Kreiner‐Møller, Anubha Mahajan, Niina Pitkänen, Raimo Joro, Alana Cavadino, Ville Huikari, Steve Franks, Maria M. Groen‐Blokhuis, Diana L. Cousminer, Julie Marsh, Terho Lehtimäki, John A. Curtin, Jesús Vioqué, Tarunveer S. Ahluwalia, Ronny Myhre, Thomas S. Price, Natàlia Vilor‐Tejedor, Loïc Yengo, Niels Grarup, Ιωάννα Ντάλλα, Wei Ang, Mustafa Atalay, Hans Bisgaard, Alexandra I. F. Blakemore, Amélie Bonnefond, Lisbeth Carstensen, Johan G. Eriksson, Claudia Flexeder, Lude Franke, Frank Geller, Mandy Geserick, Anna-Liisa Hartikainen, Claire M. A. Haworth, Joel N. Hirschhorn, Albert Hofman, Jens‐Christian Holm, Momoko Horikoshi, Jinyan Huang, Haja N. Kadarmideen, Mika Kähönen, Wieland Kieß, Hanna-Maaria Lakka, Timo A. Lakka, Alex Lewin, Liming Liang, Leo‐Pekka Lyytikäinen, Baoshan Ma, Per Magnus, Shana E. McCormack, George McMahon, Frank Mentch, Christel M. Middeldorp, Clare Murray, Katja Pahkala, Tune H. Pers, Roland Pfäffle, Dirkje S. Postma, Christopher Power, Angela Simpson, Verena Sengpiel, Carla M. T. Tiesler, Maties Torrent, André G. Uitterlinden, Joyce B. J. van Meurs, Rebecca Vinding, Johannes Waage, Eleftheria Zeggini, Babette S. Zemel, George Dedoussis, Oluf Pedersen, Philippe Froguel, Jordi Sunyer, Robert Plomin, Bo Jacobsson, Torben Hansen, Juan R. González, Adnan Čustović, Olli T. Raitakari, Craig E. Pennell, Elisabeth Widén, Dorret I. Boomsma, Gerard H. Koppelman, Sylvain Sebért, Marjo‐Riitta Järvelin, Elina Hyppönen, Mark I. McCarthy, Virpi Lindi, Harri Niinikoski, Antje Körner, Klaus Bønnelykke, Joachim Heinrich, Mads Melbye, Fernando Rivadeneira, Håkon Håkonarson, Susan M. Ring, George Davey Smith, Thorkild I. A. Sørensen, Nicholas J. Timpson, Struan F.A. Grant, Vincent W. V. Jaddoe

Bibliographic record

VenueHuman Molecular Genetics · 2015
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsnot available
FundersEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Center for Advancing Translational SciencesNational Institute of Child Health and Human DevelopmentNational Institute of Environmental Health SciencesNational Institute of Diabetes and Digestive and Kidney DiseasesNational Institute of Allergy and Infectious DiseasesNational Human Genome Research InstituteNational Institute of Mental HealthItä-Suomen YliopistoBiotechnology and Biological Sciences Research CouncilNational Heart, Lung, and Blood InstituteNational Institute for Health and Care ResearchBiocenter, University of OuluMünchner Zentrum für Gesundheitswissenschaften, Ludwig-Maximilians-Universität MünchenNIHR Imperial Biomedical Research CentreInstituto de Salud Carlos IIINational Institutes of HealthNational Institute of Neurological Disorders and StrokeGeorgia Clinical and Translational Science AllianceLung Foundation NetherlandsWellcome TrustUniversität LeipzigNederlandse Organisatie voor Wetenschappelijk OnderzoekDeutsche ForschungsgemeinschaftSvenska LäkaresällskapetSuomen KulttuurirahastoOulun YliopistoErasmus Medisch CentrumHelmholtz-Zentrum für UmweltforschungPaavo Nurmen SäätiöNovo NordiskJuho Vainion SäätiöEuropean CommissionEngineering and Physical Sciences Research CouncilGeneralitat de CatalunyaGeneralitat ValencianaErasmus Universiteit RotterdamKelaStrategiske ForskningsrådZonMwNorges ForskningsrådUniversity of OxfordKuopion Yliopistollinen SairaalaUniversity of BristolCancer Research UKAsthma and Lung UKMedical Research CouncilFundació la Marató de TV3Bundesministerium für Bildung und ForschungNational Cancer InstituteLundbeckfondenMinisterio de Ciencia e InnovaciónCanadian Institutes of Health ResearchDiabetes UKJuvenile Diabetes Research Foundation International
KeywordsBiologyGeneticsGenome-wide association studyBody mass indexGenetic associationGenomeGeneGenotypeSingle-nucleotide polymorphism

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.003
metaresearch head score (Gemma)0.004
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Meta-analysis · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: none
Teacher disagreement score0.006
Threshold uncertainty score0.014

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0030.004
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.004
Bibliometrics0.0020.003
Science and technology studies0.0000.001
Scholarly communication0.0010.000
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.032
GPT teacher head0.324
Teacher spread0.293 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designMeta-analysis
Domainnot available
GenreReview

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations371
Published2015
Admission routes1
Has abstractyes

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