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
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...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2018 |
| País: | España |
| Institución: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositorio: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:2445/120245 |
| Acceso en línea: | https://hdl.handle.net/2445/120245 |
| Access Level: | acceso abierto |
| Palabra clave: | Polimorfisme genètic Infants nadons Genetic polymorphisms Newborn infants |
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oai:recercat.cat:2445/120245 |
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España |
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| dc.title.none.fl_str_mv |
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 |
| title |
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 |
| spellingShingle |
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 Beaumont, Robin N. Polimorfisme genètic Infants nadons Genetic polymorphisms Newborn infants |
| title_short |
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 |
| title_full |
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 |
| title_fullStr |
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 |
| title_full_unstemmed |
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 |
| title_sort |
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 |
| dc.creator.none.fl_str_mv |
Beaumont, Robin N. Warrington, Nicole M. Cavadino, Alana Tyrrell, Jessica Nodzenski, Michael Horikoshi, Momoko Geller, Frank Myhre, Ronny Richmond, Rebecca C. Paternoster, Lavinia Bradfield, Jonathan P. Kreiner-Moller, Eskil Huikari, Ville Metrustry, Sarah Lunetta, Kathryn L. Painter, Jodie N. Hottenga, Jouke-Jan Allard, Catherine Barton, Sheila J. Espinosa Cardiel, Ana Marsh, Julie A. Potter, Catherine Zhang, Ge Ang, Wei Berry, Diane J. Bouchard, Luigi Das, Shikta Early Growth Genetics (EGG) Consortium Hakonarson, Hakon Heikkinen, Jani Helgeland, Øyvind Hocher, Berthold Hofman, Albert Inskip, Hazel M. Jones, Samuel E. Kogevinas, Manolis Lind, Penelope A. Marullo, Letizia Medland, Sarah E. Murray, Anna Murray, Jeffrey C. Njolstad, Pal R. Nohr, Ellen Aagard Reichetzeder, Christoph Ring, Susan M. Ruth, Katherine S. Santa Marina, Loreto Scholtens, Denise M. Sebert, Sylvain Sengpiel, Verena Tuke, Marcus A. Vaudel, Marc Weedon, Michael N. Willemsen, Gonneke Wood, Andrew R. Yaghootkar, Hanieh Muglia, Louis J. Bartels, Meike Relton, Caroline L. Pennell, Craig E. Chatzi, Leda Estivill, Xavier, 1955- Holloway, John W. Boomsma, Dorret I. Montgomery, Grant W. Murabito, Joanne M. Spector, Tim D. Power, Christine Järvelin, Marjo-Ritta Bisgaard, Hans Grant, Struan F. Sorensen, Thorkild I. A. Jaddoe, Vincent W. Jacobsson, Bo Melbye, Mads McCarthy, Mark I. Hattersley, Andrew T. Hayes, M. Geoffrey Frayling, Timothy M. Hivert, Marie-France Felix, Janine F. Hyppönen, Elina Lowe, William L. Evans, David M. Lawlor, Debbie A. Feenstra, Bjarke Freathy, Rachel M. |
| author |
Beaumont, Robin N. |
| author_facet |
Beaumont, Robin N. Warrington, Nicole M. Cavadino, Alana Tyrrell, Jessica Nodzenski, Michael Horikoshi, Momoko Geller, Frank Myhre, Ronny Richmond, Rebecca C. Paternoster, Lavinia Bradfield, Jonathan P. Kreiner-Moller, Eskil Huikari, Ville Metrustry, Sarah Lunetta, Kathryn L. Painter, Jodie N. Hottenga, Jouke-Jan Allard, Catherine Barton, Sheila J. Espinosa Cardiel, Ana Marsh, Julie A. Potter, Catherine Zhang, Ge Ang, Wei Berry, Diane J. Bouchard, Luigi Das, Shikta Early Growth Genetics (EGG) Consortium Hakonarson, Hakon Heikkinen, Jani Helgeland, Øyvind Hocher, Berthold Hofman, Albert Inskip, Hazel M. Jones, Samuel E. Kogevinas, Manolis Lind, Penelope A. Marullo, Letizia Medland, Sarah E. Murray, Anna Murray, Jeffrey C. Njolstad, Pal R. Nohr, Ellen Aagard Reichetzeder, Christoph Ring, Susan M. Ruth, Katherine S. Santa Marina, Loreto Scholtens, Denise M. Sebert, Sylvain Sengpiel, Verena Tuke, Marcus A. Vaudel, Marc Weedon, Michael N. Willemsen, Gonneke Wood, Andrew R. Yaghootkar, Hanieh Muglia, Louis J. Bartels, Meike Relton, Caroline L. Pennell, Craig E. Chatzi, Leda Estivill, Xavier, 1955- Holloway, John W. Boomsma, Dorret I. Montgomery, Grant W. Murabito, Joanne M. Spector, Tim D. Power, Christine Järvelin, Marjo-Ritta Bisgaard, Hans Grant, Struan F. Sorensen, Thorkild I. A. Jaddoe, Vincent W. Jacobsson, Bo Melbye, Mads McCarthy, Mark I. Hattersley, Andrew T. Hayes, M. Geoffrey Frayling, Timothy M. Hivert, Marie-France Felix, Janine F. Hyppönen, Elina Lowe, William L. Evans, David M. Lawlor, Debbie A. Feenstra, Bjarke Freathy, Rachel M. |
| author_role |
author |
| author2 |
Warrington, Nicole M. Cavadino, Alana Tyrrell, Jessica Nodzenski, Michael Horikoshi, Momoko Geller, Frank Myhre, Ronny Richmond, Rebecca C. Paternoster, Lavinia Bradfield, Jonathan P. Kreiner-Moller, Eskil Huikari, Ville Metrustry, Sarah Lunetta, Kathryn L. Painter, Jodie N. Hottenga, Jouke-Jan Allard, Catherine Barton, Sheila J. Espinosa Cardiel, Ana Marsh, Julie A. Potter, Catherine Zhang, Ge Ang, Wei Berry, Diane J. Bouchard, Luigi Das, Shikta Early Growth Genetics (EGG) Consortium Hakonarson, Hakon Heikkinen, Jani Helgeland, Øyvind Hocher, Berthold Hofman, Albert Inskip, Hazel M. Jones, Samuel E. Kogevinas, Manolis Lind, Penelope A. Marullo, Letizia Medland, Sarah E. Murray, Anna Murray, Jeffrey C. Njolstad, Pal R. Nohr, Ellen Aagard Reichetzeder, Christoph Ring, Susan M. Ruth, Katherine S. Santa Marina, Loreto Scholtens, Denise M. Sebert, Sylvain Sengpiel, Verena Tuke, Marcus A. Vaudel, Marc Weedon, Michael N. Willemsen, Gonneke Wood, Andrew R. Yaghootkar, Hanieh Muglia, Louis J. Bartels, Meike Relton, Caroline L. Pennell, Craig E. Chatzi, Leda Estivill, Xavier, 1955- Holloway, John W. Boomsma, Dorret I. Montgomery, Grant W. Murabito, Joanne M. Spector, Tim D. Power, Christine Järvelin, Marjo-Ritta Bisgaard, Hans Grant, Struan F. Sorensen, Thorkild I. A. Jaddoe, Vincent W. Jacobsson, Bo Melbye, Mads McCarthy, Mark I. Hattersley, Andrew T. Hayes, M. Geoffrey Frayling, Timothy M. Hivert, Marie-France Felix, Janine F. Hyppönen, Elina Lowe, William L. Evans, David M. Lawlor, Debbie A. Feenstra, Bjarke Freathy, Rachel M. |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Polimorfisme genètic Infants nadons Genetic polymorphisms Newborn infants |
| topic |
Polimorfisme genètic Infants nadons Genetic polymorphisms Newborn infants |
| description |
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. |
| publishDate |
2018 |
| dc.date.none.fl_str_mv |
2018 2018 2018 2018 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/2445/120245 |
| url |
https://hdl.handle.net/2445/120245 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Reproducció del document publicat a: http://dx.doi.org/10.1093/hmg/ddx429 Human Molecular Genetics, 2018, vol. 27, num. 4, p. 742-756 http://dx.doi.org/10.1093/hmg/ddx429 info:eu-repo/grantAgreement/EC/H2020/733206 info:eu-repo/grantAgreement/EC/H2020/648916 info:eu-repo/grantAgreement/EC/H2020/633595 info:eu-repo/grantAgreement/EC/H2020/669545 |
| dc.rights.none.fl_str_mv |
cc by (c) Beaumont et al., 2018 http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess |
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cc by (c) Beaumont et al., 2018 http://creativecommons.org/licenses/by/3.0/es/ |
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openAccess |
| dc.format.none.fl_str_mv |
15 p. application/pdf |
| dc.publisher.none.fl_str_mv |
Oxford University Press |
| publisher.none.fl_str_mv |
Oxford University Press |
| dc.source.none.fl_str_mv |
Articles publicats en revistes (ISGlobal) reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Recercat. Dipósit de la Recerca de Catalunya |
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Recercat. Dipósit de la Recerca de Catalunya |
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1869405877007548416 |
| spelling |
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 geneticsBeaumont, Robin N.Warrington, Nicole M.Cavadino, AlanaTyrrell, JessicaNodzenski, MichaelHorikoshi, MomokoGeller, FrankMyhre, RonnyRichmond, Rebecca C.Paternoster, LaviniaBradfield, Jonathan P.Kreiner-Moller, EskilHuikari, VilleMetrustry, SarahLunetta, Kathryn L.Painter, Jodie N.Hottenga, Jouke-JanAllard, CatherineBarton, Sheila J.Espinosa Cardiel, AnaMarsh, Julie A.Potter, CatherineZhang, GeAng, WeiBerry, Diane J.Bouchard, LuigiDas, ShiktaEarly Growth Genetics (EGG) ConsortiumHakonarson, HakonHeikkinen, JaniHelgeland, ØyvindHocher, BertholdHofman, AlbertInskip, Hazel M.Jones, Samuel E.Kogevinas, ManolisLind, Penelope A.Marullo, LetiziaMedland, Sarah E.Murray, AnnaMurray, Jeffrey C.Njolstad, Pal R.Nohr, Ellen AagardReichetzeder, ChristophRing, Susan M.Ruth, Katherine S.Santa Marina, LoretoScholtens, Denise M.Sebert, SylvainSengpiel, VerenaTuke, Marcus A.Vaudel, MarcWeedon, Michael N.Willemsen, GonnekeWood, Andrew R.Yaghootkar, HaniehMuglia, Louis J.Bartels, MeikeRelton, Caroline L.Pennell, Craig E.Chatzi, LedaEstivill, Xavier, 1955-Holloway, John W.Boomsma, Dorret I.Montgomery, Grant W.Murabito, Joanne M.Spector, Tim D.Power, ChristineJärvelin, Marjo-RittaBisgaard, HansGrant, Struan F.Sorensen, Thorkild I. A.Jaddoe, Vincent W.Jacobsson, BoMelbye, MadsMcCarthy, Mark I.Hattersley, Andrew T.Hayes, M. GeoffreyFrayling, Timothy M.Hivert, Marie-FranceFelix, Janine F.Hyppönen, ElinaLowe, William L.Evans, David M.Lawlor, Debbie A.Feenstra, BjarkeFreathy, Rachel M.Polimorfisme genèticInfants nadonsGenetic polymorphismsNewborn infantsGenome-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.Oxford University Press2018201820182018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion15 p.application/pdfhttps://hdl.handle.net/2445/120245Articles publicats en revistes (ISGlobal)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: http://dx.doi.org/10.1093/hmg/ddx429Human Molecular Genetics, 2018, vol. 27, num. 4, p. 742-756http://dx.doi.org/10.1093/hmg/ddx429info:eu-repo/grantAgreement/EC/H2020/733206info:eu-repo/grantAgreement/EC/H2020/648916info:eu-repo/grantAgreement/EC/H2020/633595info:eu-repo/grantAgreement/EC/H2020/669545cc by (c) Beaumont et al., 2018http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1202452026-05-29T05:05:01Z |
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15.811543 |