Evidence map›Paper›PMID 29309628›Full record

ArticleHuman molecular genetics2018

Genome-wide association study of offspring birth weight in 86 577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics.

Robin N Beaumont, Nicole M Warrington, Alana Cavadino, Jessica Tyrrell, Michael Nodzenski, Momoko Horikoshi, Frank Geller, Ronny Myhre, Rebecca C Richmond, Lavinia Paternoster and 77 more

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Article in Human molecular genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 11 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
115citing papers in PubMed, 11 pooled it
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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3 · Its place in the literature

Who cites it

115 citing papers in PubMed, 11 syntheses or guidelines pooled it.

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55 more citing papers are in PubMed but not listed here.

4 · The record

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5 · Who and what money

Authors and funding

87 authors.

Robin N BeaumontInstitute of Biomedical and Clinical Science, University of Exeter Medical School, University of Exeter, Royal Devon and Exeter Hospital, Exeter EX2 5DW, UK.
Nicole M WarringtonTranslational Research Institute, University of Queensland Diamantina Institute, Brisbane, QLD, Australia.
Alana CavadinoCentre for Environmental and Preventive Medicine, Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Jessica TyrrellInstitute of Biomedical and Clinical Science, University of Exeter Medical School, University of Exeter, Royal Devon and Exeter Hospital, Exeter EX2 5DW, UK.
Michael NodzenskiDepartment of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Momoko HorikoshiOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
Frank GellerDepartment of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
Ronny MyhreDivision of Epidemiology, Department of Genes and Environment, Norwegian Institute of Public Health, Oslo, Norway.
Rebecca C RichmondMedical Research Council Integrative Epidemiology Unit at the University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK.
Lavinia PaternosterMedical Research Council Integrative Epidemiology Unit at the University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK.
Jonathan P BradfieldCenter for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Eskil Kreiner-MøllerCopenhagen Prospective Studies on Asthma in Childhood (COPSAC), Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
Ville HuikariInstitute of Health Sciences, University of Oulu, Oulu, Finland.
Sarah MetrustryDepartment of Twin Research, King's College London, St. Thomas' Hospital, London, UK.
Kathryn L LunettaDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Jodie N PainterQIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Herston, QLD 4029, Australia.
Jouke-Jan HottengaEMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
Catherine AllardCentre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC, Canada.
Sheila J BartonMedical Research Council Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
Ana EspinosaPompeu Fabra University (UPF), Barcelona, Spain.
Julie A MarshDivision of Obstetrics and Gynaecology, The University of Western Australia, Perth, Australia.
Catherine PotterInstitute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle upon Tyne NE1 3BZ, UK.
Ge ZhangHuman Genetics Division, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Wei AngDivision of Obstetrics and Gynaecology, The University of Western Australia, Perth, Australia.
Diane J BerryPopulation, Policy and Practice, UCL Great Ormond Street Institute of Child Health, University College London, London, UK.
Luigi BouchardCentre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC, Canada.
Shikta DasPopulation, Policy and Practice, UCL Great Ormond Street Institute of Child Health, University College London, London, UK.
Early Growth Genetics (EGG) Consortium
Hakon HakonarsonCenter for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Jani HeikkinenFIMM Institute for Molecular Medicine Finland, Helsinki University, Helsinki FI-00014, Finland.
Øyvind HelgelandDepartment of Clinical Science, KG Jebsen Center for Diabetes Research, University of Bergen, Bergen, Norway.
Berthold HocherThe First Affiliated Hospital of Jinan University, Guangzhou 510630, China.
Albert HofmanDepartment of Epidemiology, Erasmus MC, University Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands.
Hazel M InskipMedical Research Council Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
Samuel E JonesInstitute of Biomedical and Clinical Science, University of Exeter Medical School, University of Exeter, Royal Devon and Exeter Hospital, Exeter EX2 5DW, UK.
Manolis KogevinasPompeu Fabra University (UPF), Barcelona, Spain.
Penelope A LindQIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Herston, QLD 4029, Australia.
Letizia MarulloGenetic Section, Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.
Sarah E MedlandQIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Herston, QLD 4029, Australia.
Anna MurrayInstitute of Biomedical and Clinical Science, University of Exeter Medical School, University of Exeter, Royal Devon and Exeter Hospital, Exeter EX2 5DW, UK.
Jeffrey C MurrayDepartment of Pediatrics, University of Iowa, Iowa City, IA, USA.
Pål R NjølstadDepartment of Clinical Science, KG Jebsen Center for Diabetes Research, University of Bergen, Bergen, Norway.
Ellen A NohrResearch Unit of Obstetrics & Gynecology, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.
Christoph ReichetzederInstitute of Nutritional Science, University of Potsdam, Potsdam, Germany.
Susan M RingMedical Research Council Integrative Epidemiology Unit at the University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK.
Katherine S RuthInstitute of Biomedical and Clinical Science, University of Exeter Medical School, University of Exeter, Royal Devon and Exeter Hospital, Exeter EX2 5DW, UK.
Loreto Santa-MarinaISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.
Denise M ScholtensDepartment of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Sylvain SebertInstitute of Health Sciences, University of Oulu, Oulu, Finland.
Verena SengpielDepartment of Obstetrics and Gynecology, Sahlgrenska Academy, Sahgrenska University Hospital, Gothenburg, Sweden.
Marcus A TukeInstitute of Biomedical and Clinical Science, University of Exeter Medical School, University of Exeter, Royal Devon and Exeter Hospital, Exeter EX2 5DW, UK.
Marc VaudelDepartment of Clinical Science, KG Jebsen Center for Diabetes Research, University of Bergen, Bergen, Norway.
Michael N WeedonInstitute of Biomedical and Clinical Science, University of Exeter Medical School, University of Exeter, Royal Devon and Exeter Hospital, Exeter EX2 5DW, UK.
Gonneke WillemsenEMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
Andrew R WoodInstitute of Biomedical and Clinical Science, University of Exeter Medical School, University of Exeter, Royal Devon and Exeter Hospital, Exeter EX2 5DW, UK.
Hanieh YaghootkarInstitute of Biomedical and Clinical Science, University of Exeter Medical School, University of Exeter, Royal Devon and Exeter Hospital, Exeter EX2 5DW, UK.
Louis J MugliaCenter for Prevention of Preterm Birth, Perinatal Institute, Cincinnati Children's Hospital Medical Center, OH, USA.
Meike BartelsEMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
Caroline L ReltonMedical Research Council Integrative Epidemiology Unit at the University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK.
Craig E PennellDivision of Obstetrics and Gynaecology, The University of Western Australia, Perth, Australia.
Leda ChatziDepartment of Social Medicine, University of Crete, Crete, Greece.
Xavier EstivillPompeu Fabra University (UPF), Barcelona, Spain.
John W HollowayHuman Development & Health, Faculty of Medicine, University of Southampton, Southampton, UK.
Dorret I BoomsmaEMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
Grant W MontgomeryQIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Herston, QLD 4029, Australia.
Joanne M MurabitoFramingham Heart Study, Framingham, MA, USA.
Tim D SpectorDepartment of Twin Research, King's College London, St. Thomas' Hospital, London, UK.
Christine PowerPopulation, Policy and Practice, UCL Great Ormond Street Institute of Child Health, University College London, London, UK.
Marjo-Ritta JärvelinInstitute of Health Sciences, University of Oulu, Oulu, Finland.
Hans BisgaardCopenhagen Prospective Studies on Asthma in Childhood (COPSAC), Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
Struan F A GrantCenter for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Thorkild I A SørensenMedical Research Council Integrative Epidemiology Unit at the University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK.
Vincent W JaddoeThe Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands.
Bo JacobssonDivision of Epidemiology, Department of Genes and Environment, Norwegian Institute of Public Health, Oslo, Norway.
Mads MelbyeDepartment of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
Mark I McCarthyOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
Andrew T HattersleyInstitute of Biomedical and Clinical Science, University of Exeter Medical School, University of Exeter, Royal Devon and Exeter Hospital, Exeter EX2 5DW, UK.
M Geoffrey HayesDivision of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Timothy M FraylingInstitute of Biomedical and Clinical Science, University of Exeter Medical School, University of Exeter, Royal Devon and Exeter Hospital, Exeter EX2 5DW, UK.
Marie-France HivertDepartment of Population Medicine, Harvard Pilgrim Health Care Institute, Harvard Medical School, Boston, MA, USA.
Janine F FelixThe Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands.
Elina HyppönenPopulation, Policy and Practice, UCL Great Ormond Street Institute of Child Health, University College London, London, UK.
William L LoweDivision of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
David M EvansTranslational Research Institute, University of Queensland Diamantina Institute, Brisbane, QLD, Australia.
Debbie A LawlorMedical Research Council Integrative Epidemiology Unit at the University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK.
Bjarke FeenstraDepartment of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
Rachel M FreathyInstitute of Biomedical and Clinical Science, University of Exeter Medical School, University of Exeter, Royal Devon and Exeter Hospital, Exeter EX2 5DW, UK.

Funding

Translational Research Support CoreP30ES013508 · NIEHS · UNIVERSITY OF PENNSYLVANIA · PI Trevor M Penning · 2006 to 2026
$35.3M
Metabolomic and Epigenomic Mechanisms in Developmental Overnutrition.R01DK103246 · NIDDK · UNIVERSITY OF BRISTOL · PI LAWLOR, DEBORAH ANNE · 2014 to 2018
$2.2M
Exceptional Aging Across the Life Span: Framingham StudyR01AG029451 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI MURABITO, JOANNE M · 2008 to 2011
$1.3M
Maternal overnutrition and offspring fat mass, metabolic and vascular function.R01DK077659 · NIDDK · UNIVERSITY OF BRISTOL · PI LAWLOR, DEBORAH ANNE · 2006 to 2009
$986k
British Heart Foundation PG/09/023/26806British Heart Foundation RG/15/17/31749Department of Health PHCS/C4/4/016European Research Council 648916Medical Research Council G0601653Medical Research Council G1001799Medical Research Council MC_QA137853Medical Research Council MC_UU_12011/4Medical Research Council MC_UU_12013/2Medical Research Council MC_UU_12013/4Medical Research Council MC_UU_12013/5Medical Research Council MR/M005070/1Medical Research Council MR/N01104X/1Medical Research Council MR/N01104X/2NIA NIH HHS R01 AG029451NIDDK NIH HHS R01 DK077659NIDDK NIH HHS R01 DK103246NIEHS NIH HHS P30 ES013508Wellcome Trust 104150
6 · The paper itself

Abstract

Genome-wide association studies of birth weight have focused on fetal genetics, whereas relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86 577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother-child pairs to quantify the separate maternal and fetal genetic effects. Maternal SNPs at 10 loci (MTNR1B, HMGA2, SH2B3, KCNAB1, L3MBTL3, GCK, EBF1, TCF7L2, ACTL9, CYP3A7) were associated with offspring birth weight at P < 5 × 10-8. In SEM analyses, at least 7 of the 10 associations were consistent with effects of the maternal genotype acting via the intrauterine environment, rather than via effects of shared alleles with the fetus. Variants, or correlated proxies, at many of the loci had been previously associated with adult traits, including fasting glucose (MTNR1B, GCK and TCF7L2) and sex hormone levels (CYP3A7), and one (EBF1) with gestational duration. The identified associations indicate that genetic effects on maternal glucose, cytochrome P450 activity and gestational duration, and potentially on maternal blood pressure and immune function, are relevant for fetal growth. Further characterization of these associations in mechanistic and causal analyses will enhance understanding of the potentially modifiable maternal determinants of fetal growth, with the goal of reducing the morbidity and mortality associated with low and high birth weights.

Indexed as

ActinsAdaptor Proteins, Signal TransducingAllelesBirth WeightCytochrome P-450 CYP3ADNA-Binding ProteinsFemaleGenetic VariationGenome-Wide Association StudyGenotypeGerminal Center KinasesGestational AgeHMGA2 ProteinHumansIntracellular Signaling Peptides and ProteinsKv1.3 Potassium ChannelActinsACTL9 protein, humanAdaptor Proteins, Signal TransducingCYP3A7 protein, humanCytochrome P-450 CYP3ADNA-Binding ProteinsEBF1 protein, humanGerminal Center KinasesHMGA2 ProteinHMGA2 protein, humanIntracellular Signaling Peptides and ProteinsKCNAB1 protein, humanKv1.3 Potassium ChannelL3MBTL3 protein, humanMTNR1B protein, humanProteinsProtein Serine-Threonine KinasesReceptor, Melatonin, MT2SH2B3 protein, humanTrans-ActivatorsTranscription Factor 7-Like 2 Protein

Identifiers

PMID29309628
PMCPMC5886200

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