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.

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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 (author)

Warrington, Nicole M (author)

Cavadino, Alana (author)

Tyrrell, Jessica (author)

Nodzenski, Michael (author)

Horikoshi, Momoko (author)

Geller, Frank (author)

Myhre, Ronny (author)

Richmond, Rebecca C (author)

Paternoster, Lavinia (author)

Bradfield, Jonathan P (author)

Kreiner-Møller, Eskil (author)

Huikari, Ville (author)

Metrustry, Sarah (author)

Lunetta, Kathryn L (author)

Painter, Jodie N (author)

Hottenga, Jouke-Jan (author)

Allard, Catherine (author)

Barton, Sheila J (author)

Espinosa, Ana (author)

Marsh, Julie A (author)

Potter, Catherine (author)

Zhang, Ge (author)

Ang, Wei (author)

Berry, Diane J (author)

Bouchard, Luigi (author)

Das, Shikta (author)

Hakonarson, Hakon (author)

Heikkinen, Jani (author)

Helgeland, Øyvind (author)

Hocher, Berthold (author)

Hofman, Albert (author)

Inskip, Hazel M (author)

Jones, Samuel E (author)

Kogevinas, Manolis (author)

Lind, Penelope A (author)

Marullo, Letizia (author)

Medland, Sarah E (author)

Murray, Anna (author)

Murray, Jeffrey C (author)

Njølstad, Pål R (author)

Nohr, Ellen A (author)

Reichetzeder, Christoph (author)

Ring, Susan M (author)

Ruth, Katherine S (author)

Santa-Marina, Loreto (author)

Scholtens, Denise M (author)

Sebert, Sylvain (author)

Sengpiel, Verena, 1977 (author): Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för obstetrik och gynekologi,Institute of Clinical Sciences, Department of Obstetrics and Gynecology

Tuke, Marcus A (author)

Vaudel, Marc (author)

Weedon, Michael N (author)

Willemsen, Gonneke (author)

Wood, Andrew R (author)

Yaghootkar, Hanieh (author)

Muglia, Louis J (author)

Bartels, Meike (author)

Relton, Caroline L (author)

Pennell, Craig E (author)

Chatzi, Leda (author)

Estivill, Xavier (author)

Holloway, John W (author)

Boomsma, Dorret I (author)

Montgomery, Grant W (author)

Murabito, Joanne M (author)

Spector, Tim D (author)

Power, Christine (author)

Järvelin, Marjo-Ritta (author)

Bisgaard, Hans (author)

Grant, Struan Fa (author)

Sørensen, Thorkild Ia (author)

Jaddoe, Vincent W (author)

Jacobsson, Bo, 1960 (author): Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för obstetrik och gynekologi,Institute of Clinical Sciences, Department of Obstetrics and Gynecology

Melbye, Mads (author)

McCarthy, Mark I (author)

Hattersley, Andrew T (author)

Hayes, M Geoffrey (author)

Frayling, Timothy M (author)

Hivert, Marie-France (author)

Felix, Janine F (author)

Hyppönen, Elina (author)

Lowe, William L (author)

Evans, David M (author)

Lawlor, Debbie A (author)

Feenstra, Bjarke (author)

Freathy, Rachel M (author)

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(creator_code:org_t)

2018-01-03
2018
English.
In: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 1460-2083 .- 0964-6906. ; 27:4, s. 742-756

Related links:: https://academic.oup...; show more...; https://gup.ub.gu.se...; https://doi.org/10.1...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

Genome-wide association studies (GWAS) of birth weight have focused on fetal genetics, while 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<5x10-8. 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 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.

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By the author/editor: Beaumont, Robin ...; Warrington, Nico ...; Cavadino, Alana; Tyrrell, Jessica; Nodzenski, Micha ...; Horikoshi, Momok ...; show more...; Geller, Frank; Myhre, Ronny; Richmond, Rebecc ...; Paternoster, Lav ...; Bradfield, Jonat ...; Kreiner-Møller, ...; Huikari, Ville; Metrustry, Sarah; Lunetta, Kathryn ...; Painter, Jodie N; Hottenga, Jouke- ...; Allard, Catherin ...; Barton, Sheila J; Espinosa, Ana; Marsh, Julie A; Potter, Catherin ...; Zhang, Ge; Ang, Wei; Berry, Diane J; Bouchard, Luigi; Das, Shikta; Hakonarson, Hako ...; Heikkinen, Jani; Helgeland, Øyvin ...; Hocher, Berthold; Hofman, Albert; Inskip, Hazel M; Jones, Samuel E; Kogevinas, Manol ...; Lind, Penelope A; Marullo, Letizia; Medland, Sarah E; Murray, Anna; Murray, Jeffrey ...; Njølstad, Pål R; Nohr, Ellen A; Reichetzeder, Ch ...; Ring, Susan M; Ruth, Katherine ...; Santa-Marina, Lo ...; Scholtens, Denis ...; Sebert, Sylvain; Sengpiel, Verena ...; Tuke, Marcus A; Vaudel, Marc; Weedon, Michael ...; Willemsen, Gonne ...; Wood, Andrew R; Yaghootkar, Hani ...; Muglia, Louis J; Bartels, Meike; Relton, Caroline ...; Pennell, Craig E; Chatzi, Leda; Estivill, Xavier; Holloway, John W; Boomsma, Dorret ...; Montgomery, Gran ...; Murabito, Joanne ...; Spector, Tim D; Power, Christine; Järvelin, Marjo- ...; Bisgaard, Hans; Grant, Struan Fa; Sørensen, Thorki ...; Jaddoe, Vincent ...; Jacobsson, Bo, 1 ...; Melbye, Mads; McCarthy, Mark I; Hattersley, Andr ...; Hayes, M Geoffre ...; Frayling, Timoth ...; Hivert, Marie-Fr ...; Felix, Janine F; Hyppönen, Elina; Lowe, William L; Evans, David M; Lawlor, Debbie A; Feenstra, Bjarke; Freathy, Rachel ...; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Obstetrics Gynae ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...

Articles in the publication: Human molecular ...

By the university: University of Gothenburg

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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.

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