Rxivist logo

Genome-wide association study of offspring birth weight in 86,577 women highlights maternal genetic effects that are independent of fetal genetics

By RN Beaumont, Nicole M. Warrington, Alana Cavadino, J Tyrrell, Michael Nodzenski, Momoko Horikoshi, Frank Geller, Ronny Myhre, Rebecca C. Richmond, Lavinia Paternoster, Jonathan P. Bradfield, Eskil Kreiner-Møller, 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, Early Growth Genetics (EGG) Consortium, Hakon Hakonarson, Jani Heikkinen, Øyvind 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, Pål R. Njølstad, 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 Järvelin, Hans Bisgaard, Struan F.A. Grant, Thorkild IA Sørensen, Vincent W. Jaddoe, Bo Jacobsson, Mads Melbye, Mark I. McCarthy, Andrew T Hattersley, M. Geoffrey Hayes, TM Frayling, Marie-France Hivert, Janine F. Felix, Elina Hyppönen, William L Lowe, DM Evans, DA Lawlor, Bjarke Feenstra, RM Freathy

Posted 11 Dec 2015
bioRxiv DOI: 10.1101/034207 (published DOI: 10.1093/hmg/ddx429)

Genome-wide association studies (GWAS) of birth weight have focused on fetal genetics, while relatively little is known about how maternal genetic variation influences fetal growth. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed GWAS 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 and CYP3A7) showed evidence of association with offspring birth weight at P<5x10-8. The SEM analyses showed 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 effects of maternal glucose, cytochrome P450 activity and gestational duration, and potential effects of maternal blood pressure and immune function on fetal growth. Further characterization of these associations, for example 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.

Download data

  • Downloaded 1,152 times
  • Download rankings, all-time:
    • Site-wide: 10,689 out of 100,957
    • In genetics: 713 out of 5,023
  • Year to date:
    • Site-wide: 64,755 out of 100,957
  • Since beginning of last month:
    • Site-wide: 61,404 out of 100,957

Altmetric data

Downloads over time

Distribution of downloads per paper, site-wide


Sign up for the Rxivist weekly newsletter! (Click here for more details.)


  • 20 Oct 2020: Support for sorting preprints using Twitter activity has been removed, at least temporarily, until a new source of social media activity data becomes available.
  • 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
  • 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
  • 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
  • 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
  • 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
  • 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
  • 22 Jan 2019: Nature just published an article about Rxivist and our data.
  • 13 Jan 2019: The Rxivist preprint is live!