Robin N. Beaumont, Nicole M. Warrington, Alana Cavadino, Jessica Tyrrell, Michael Nodzenski, Momoko Horikoshi, Frank Geller, Ronny Myhre, Rebecca C. Richmond, Lavinia Paternoster, Jonathan P. Bradfield, Eskil Kreiner-Moller, Ville Huikari, Sarah Metrustry, Kathryn L. Lunetta, Jodie N. Painter, Jouke-Jan Hottenga, Catherine Allard, Sheila J. Barton, Ana Espinosa, Julie A. Marsh, Catherine Potter, Ge Zhang, Wei Ang, Diane J. Berry, Luigi Bouchard, Shikta Das, Hakon Hakonarson, Jani Heikkinen, Oyvind Helgeland, Berthold Hocher, Albert Hofman, Hazel M. Inskip, Samuel E. Jones, Manolis Kogevinas, Penelope A. Lind, Letizia Marullo, Sarah E. Medland, Anna Murray, Jeffrey C. Murray, Pal R. Njolstad, Ellen A. Nohr, Christoph Reichetzeder, Susan M. Ring, Katherine S. Ruth, Loreto Santa-Marina, Denise M. Scholtens, Sylvain Sebert, Verena Sengpiel, Marcus A. Tuke, Marc Vaudel, Michael N. Weedon, Gonneke Willemsen, Andrew R. Wood, Hanieh Yaghootkar, Louis J. Muglia, Meike Bartels, Caroline L. Relton, Craig E. Pennell, Leda Chatzi, Xavier Estivill, John W. Holloway, Dorret I. Boomsma, Grant W. Montgomery, Joanne M. Murabito, Tim D. Spector, Christine Power, Marjo-Ritta Jarvelin, Hans Bisgaard, Struan F. A. Grant, Thorkild I. A. Sorensen, Vincent W. Jaddoe, Bo Jacobsson, Mads Melbye, Mark I. McCarthy, Andrew T. Hattersley, M. Geoffrey Hayes, Timothy M. Frayling, Marie-France Hivert, Janine F. Felix, Elina Hypponen, William L. Lowe, David M. Evans, Debbie A. Lawlor, Bjarke Feenstra, Rachel M. Freathy
- 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 x 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 beenGenome-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 x 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.…
MetadatenAuthor details: | Robin N. Beaumont, Nicole M. Warrington, Alana CavadinoORCiD, Jessica Tyrrell, Michael Nodzenski, Momoko Horikoshi, Frank GellerORCiD, Ronny Myhre, Rebecca C. Richmond, Lavinia Paternoster, Jonathan P. Bradfield, Eskil Kreiner-Moller, Ville Huikari, Sarah Metrustry, Kathryn L. Lunetta, Jodie N. Painter, Jouke-Jan HottengaORCiD, Catherine AllardORCiD, Sheila J. Barton, Ana Espinosa, Julie A. Marsh, Catherine Potter, Ge Zhang, Wei Ang, Diane J. Berry, Luigi Bouchard, Shikta Das, Hakon Hakonarson, Jani HeikkinenORCiD, Oyvind Helgeland, Berthold HocherORCiDGND, Albert Hofman, Hazel M. Inskip, Samuel E. Jones, Manolis KogevinasORCiD, Penelope A. Lind, Letizia Marullo, Sarah E. Medland, Anna MurrayORCiD, Jeffrey C. Murray, Pal R. Njolstad, Ellen A. Nohr, Christoph ReichetzederORCiDGND, Susan M. Ring, Katherine S. Ruth, Loreto Santa-Marina, Denise M. Scholtens, Sylvain Sebert, Verena Sengpiel, Marcus A. Tuke, Marc Vaudel, Michael N. Weedon, Gonneke WillemsenORCiD, Andrew R. Wood, Hanieh Yaghootkar, Louis J. Muglia, Meike Bartels, Caroline L. Relton, Craig E. Pennell, Leda Chatzi, Xavier EstivillORCiD, John W. Holloway, Dorret I. Boomsma, Grant W. Montgomery, Joanne M. Murabito, Tim D. Spector, Christine Power, Marjo-Ritta Jarvelin, Hans BisgaardORCiD, Struan F. A. Grant, Thorkild I. A. Sorensen, Vincent W. Jaddoe, Bo JacobssonORCiD, Mads Melbye, Mark I. McCarthy, Andrew T. Hattersley, M. Geoffrey Hayes, Timothy M. Frayling, Marie-France Hivert, Janine F. Felix, Elina HypponenORCiD, William L. Lowe, David M. Evans, Debbie A. Lawlor, Bjarke Feenstra, Rachel M. FreathyORCiD |
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DOI: | https://doi.org/10.1093/hmg/ddx429 |
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ISSN: | 0964-6906 |
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ISSN: | 1460-2083 |
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Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/29309628 |
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Title of parent work (English): | Human molecular genetics |
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Publisher: | Oxford Univ. Press |
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Place of publishing: | Oxford |
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Publication type: | Article |
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Language: | English |
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Date of first publication: | 2018/01/03 |
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Publication year: | 2018 |
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Creating corporation: | Early Growth Genetics EGG |
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Release date: | 2022/01/19 |
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Volume: | 27 |
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Issue: | 4 |
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Number of pages: | 15 |
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First page: | 742 |
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Last Page: | 756 |
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Funding institution: | European Regional Development Fund (ERDF)European Union (EU); European Social Fund (ESF) Convergence Programme for Cornwall and the Isles of Scilly; European Research Council (ERC)European Research Council (ERC) [SZ-245 50371-GLUCOSEGENES-FP7-IDEAS-ERC, ERC-2014-CoG-648916]; University of Bergen, KG Jebsen; University of Bergen, Helse Vest; Wellcome Trust Senior Investigator AwardsWellcome Trust [WT098395, WT098381]; National Institute for Health Research (NIHR) Senior Investigator AwardNational Institute for Health Research (NIHR) [NF-SI-0611-10219]; Sir Henry Dale Fellowship (Wellcome Trust); Sir Henry Dale Fellowship (Royal Society grant) [WT104150]; 4-year studentship [WT083431MF]; European Research Council under the European US National Institute of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01 DK10324]; Wellcome Trust GWAS grantWellcome Trust [WT088806]; NIHR Senior Investigator Award [NF-SI-0611-10196]; Wellcome Trust Institutional Strategic Support AwardWellcome Trust [WT097835MF]; Diabetes Research and Wellness Foundation Non-Clinical Fellowship; Australian National Health and Medical Research Council Early Career FellowshipNational Health and Medical Research Council of Australia [APP1104818]; Daniel B. Burke Endowed Chair for Diabetes Research; UK Medical Research Council Unit grants [MC_UU_12013_5, MC_UU_12013_4]; Medical Research CouncilMedical Research Council UK (MRC) [MR/M005070/1]; Australian Research Council Future FellowshipAustralian Research Council [FT130101709, FT110100548]; NIHR Oxford Biomedical Research Centre (BRC); Oak Foundation Fellowship; Novo Nordisk FoundationNovo Nordisk Foundation [12955]; Canadian Diabetes Association; Institute of Genetics-Canadian Institute of Health Research (CIHR); CIHR-Frederick Banting and Charles Best Canada Graduate ScholarshipsCanadian Institutes of Health Research (CIHR); FRQS; Netherlands Organization for Health Research and DevelopmentNetherlands Organization for Health Research and Development [ZonMw-VIDI 016.136.361]; National Institute on AgingUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Aging (NIA) [R01AG29451]; PRIN funds of the University of Ferrara; European Foundation for the Study of Diabetes (EFSD) Albert Renold Travel Fellowships for Young Scientists; ENGAGE Exchange and Mobility Program for ENGAGE training funds, ENGAGE project [HEALTH-F4-2007-201413]; ESRCEconomic & Social Research Council (ESRC) [RES-060-23-0011]; National Institute of Health ResearchNational Institute for Health Research (NIHR); Australian NHMRC Fellowships SchemeNational Health and Medical Research Council of Australia [619667]; Charity Open Access Fund (COAF) |
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Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Biochemie und Biologie |
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DDC classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
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Peer review: | Referiert |
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Publishing method: | Open Access / Hybrid Open-Access |
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External remark: | Zweitveröffentlichung in der Schriftenreihe Postprints der Universität Potsdam : Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe ; 628 |
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