Rxivist logo

Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 63,046 bioRxiv papers from 279,617 authors.

Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors

By Nicole M. Warrington, Robin N Beaumont, Momoko Horikoshi, Felix R Day, Øyvind Helgeland, Charles Laurin, Jonas Bacelis, Shouneng Peng, Ke Hao, Bjarke Feenstra, Andrew R Wood, Anubha Mahajan, Jessica Tyrrell, Neil R Robertson, N William Rayner, Zhen Qiao, Gunn-Helen Øiseth Moen, Marc Vaudel, Carmen J. Marsit, Jia Chen, Michael Nodzenski, Theresia M. Schnurr, Mohammad H Zafarmand, Jonathan P. Bradfield, Niels Grarup, Marjolein N Kooijman, Ruifang Li-Gao, Frank Geller, Tarunveer S. Ahluwalia, Lavinia Paternoster, Rico Rueedi, Ville Huikari, Jouke-Jan Hottenga, Leo-Pekka Lyytikäinen, Alana Cavadino, Sarah Metrustry, Diana L Cousminer, Ying Wu, Elisabeth Thiering, Carol A Wang, Christian T Have, Natalia Vilor-Tejedor, Peter K Joshi, Jodie N Painter, Ioanna Ntalla, Ronny Myhre, Niina Pitkänen, Elisabeth M van Leeuwen, Raimo Joro, Vasiliki Lagou, Rebecca C. Richmond, Ana Espinosa, Sheila J. Barton, Hazel M Inskip, John W. Holloway, Loreto Santa-Marina, Xavier Estivill, Wei Ang, Julie A Marsh, Christoph Reichetzeder, Letizia Marullo, Berthold Hocher, Kathryn L. Lunetta, Joanne M. Murabito, Caroline L Relton, Manolis Kogevinas, Leda Chatzi, Catherine Allard, Luigi Bouchard, Marie-France Hivert, Ge Zhang, Louis J Muglia, Jani Heikkinen, Early Growth Genetics (EGG) Consortium, Camilla S Morgen, Antoine HC van Kampen, Barbera DC van Schaik, Frank D Mentch, Claudia Langenberg, Jian’an Luan, Robert A Scott, Jing Hua Zhao, Gibran Hemani, Susan M. Ring, Amanda J Bennett, Kyle J Gaulton, Juan Fernandez-Tajes, Natalie R van Zuydam, Carolina Medina-Gomez, Hugoline G de Haan, Frits R Rosendaal, Zoltán Kutalik, Pedro Marques-Vidal, Shikta Das, Gonneke Willemsen, Hamdi Mbarek, Martina Müller-Nurasyid, Marie Standl, Emil V. R. Appel, Cilius E Fonvig, Caecilie Trier, Catharina EM van Beijsterveldt, Mario Murcia, Mariona Bustamante, Sílvia Bonas-Guarch, David M Hougaard, Josep M. Mercader, Allan Linneberg, Katharina E Schraut, Penelope A Lind, Sarah E Medland, Beverley M Shields, Bridget A. Knight, Jin-Fang Chai, Kalliope Panoutsopoulou, Meike Bartels, Friman Sánchez, Jacob Stokholm, David Torrents, Rebecca K. Vinding, Sara M Willems, Mustafa Atalay, Bo L Chawes, Peter Kovacs, Inga Prokopenko, Marcus A Tuke, Hanieh Yaghootkar, Katherine S Ruth, Samuel E Jones, Po-Ru Loh, Anna Murray, Michael N Weedon, Anke Tönjes, Michael Stumvoll, Kim F. Michaelsen, Aino-Maija Eloranta, Timo A. Lakka, Cornelia M. van Duijn, Wieland Kiess, Antje Körner, Harri Niinikoski, Katja Pahkala, Olli T Raitakari, Bo Jacobsson, Eleftheria Zeggini, George V Dedoussis, Yik-Ying Teo, Seang-Mei Saw, Grant W. Montgomery, Harry Campbell, James F Wilson, Tanja GM Vrijkotte, Martine Vrijheid, Eco JCN de Geus, M. Geoffrey Hayes, Haja N Kadarmideen, Jens-Christian Holm, Lawrence J. Beilin, Craig E. Pennell, Joachim Heinrich, Linda S Adair, Judith B Borja, Karen L Mohlke, Johan G. Eriksson, Elisabeth E Widén, Andrew T Hattersley, Tim D Spector, Mika Kähönen, Jorma S Viikari, Terho Lehtimäki, Dorret I Boomsma, Sylvain Sebert, Peter Vollenweider, Thorkild IA Sørensen, Hans Bisgaard, Klaus Bønnelykke, Jeffrey C Murray, Mads Melbye, Ellen A Nohr, Dennis O. Mook-Kanamori, Fernando Rivadeneira, Albert Hofman, Janine F. Felix, Vincent W.V. Jaddoe, Torben Hansen, Charlotta Pisinger, Allan A Vaag, Oluf Pedersen, André G. Uitterlinden, Marjo-Riitta Järvelin, Christine Power, Elina Hyppönen, Denise M. Scholtens, William L Lowe, George Davey Smith, Nicholas J. Timpson, Andrew P Morris, Nicholas J Wareham, Hakon Hakonarson, Struan F.A. Grant, Timothy M Frayling, Debbie A Lawlor, Pål R. Njølstad, Stefan Johansson, Ken K. Ong, Mark I McCarthy, John RB Perry, David M Evans, Rachel M. Freathy

Posted 17 Oct 2018
bioRxiv DOI: 10.1101/442756 (published DOI: 10.1038/s41588-019-0403-1)

Birth weight (BW) variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. These associations have been proposed to reflect the lifelong consequences of an adverse intrauterine environment. In earlier work, we demonstrated that much of the negative correlation between BW and adult cardio-metabolic traits could instead be attributable to shared genetic effects. However, that work and other previous studies did not systematically distinguish the direct effects of an individual's own genotype on BW and subsequent disease risk from indirect effects of their mother's correlated genotype, mediated by the intrauterine environment. Here, we describe expanded genome-wide association analyses of own BW (n=321,223) and offspring BW (n=230,069 mothers), which identified 278 independent association signals influencing BW (214 novel). We used structural equation modelling to decompose the contributions of direct fetal and indirect maternal genetic influences on BW, implicating fetal- and maternal-specific mechanisms. We used Mendelian randomization to explore the causal relationships between factors influencing BW through fetal or maternal routes, for example, glycemic traits and blood pressure. Direct fetal genotype effects dominate the shared genetic contribution to the association between lower BW and higher type 2 diabetes risk, whereas the relationship between lower BW and higher later blood pressure (BP) is driven by a combination of indirect maternal and direct fetal genetic effects: indirect effects of maternal BP-raising genotypes act to reduce offspring BW, but only direct fetal genotype effects (once inherited) increase the offspring's later BP. Instrumental variable analysis using maternal BW-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring BP. In successfully separating fetal from maternal genetic effects, this work represents an important advance in genetic studies of perinatal outcomes, and shows that the association between lower BW and higher adult BP is attributable to genetic effects, and not to intrauterine programming.

Download data

  • Downloaded 988 times
  • Download rankings, all-time:
    • Site-wide: 7,244 out of 63,046
    • In genetics: 565 out of 3,574
  • Year to date:
    • Site-wide: 2,701 out of 63,046
  • Since beginning of last month:
    • Site-wide: 19,540 out of 63,046

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


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


News