New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism

Momoko Horikoshi, Hanieh Yaghootkar, Dennis O. Mook-Kanamori, Ulla Sovio, H. Rob Taal, Branwen J. Hennig, Jonathan P. Bradfield, Beate St Pourcain, David M. Evans, Pimphen Charoen, Marika Kaakinen, Diana L. Cousminer, Terho Lehtimäki, Eskil Kreiner-Møller, Nicole M. Warrington, Mariona Bustamante, Bjarke Feenstra, Diane J. Berry, Elisabeth Thiering, Thiemo PfabSheila J. Barton, Beverley M. Shields, Marjan Kerkhof, Elisabeth M. Van Leeuwen, Anthony J. Fulford, Zoltán Kutalik, Jing Hua Zhao, Marcel Den Hoed, Anubha Mahajan, Virpi Lindi, Liang Kee Goh, Jouke Jan Hottenga, Ying Wu, Olli T. Raitakari, Marie N. Harder, Aline Meirhaeghe, Ioanna Ntalla, Rany M. Salem, Karen A. Jameson, Kaixin Zhou, Dorota M. Monies, Vasiliki Lagou, Mirna Kirin, Jani Heikkinen, Linda S. Adair, Fowzan S. Alkuraya, Ali Al-Odaib, Philippe Amouyel, Ehm Astrid Andersson, Amanda J. Bennett, Alexandra I.F. Blakemore, Jessica L. Buxton, Jean Dallongeville, Shikta Das, Eco J.C. De Geus, Xavier P. Estivill, Claudia Flexeder, Philippe Froguel, Frank Geller, Keith M. Godfrey, Frédéric Gottrand, Christopher J. Groves, Torben Hansen, Joel N. Hirschhorn, Albert Hofman, Mads V. Hollegaard, David M. Hougaard, Elina Hyppönen, Hazel M. Inskip, Aaron Isaacs, Torben Jørgensen, Christina Kanaka-Gantenbein, John P. Kemp, Wieland Kiess, Tuomas O. Kilpeläinen, Norman Klopp, Bridget A. Knight, Christopher W. Kuzawa, George Mcmahon, John P. Newnham, Harri Niinikoski, Ben A. Oostra, Louise Pedersen, Dirkje S. Postma, Susan M. Ring, Fernando Rivadeneira, Neil R. Robertson, Sylvain Sebert, Olli Simell, Torsten Slowinski, Carla M.T. Tiesler, Anke Tönjes, Allan Vaag, Jorma S. Viikari, Jacqueline M. Vink, Nadja Hawwa Vissing, Nicholas J. Wareham, Gonneke Willemsen, Daniel R. Witte, Haitao Zhang, Jianhua Zhao, James F. Wilson, Michael Stumvoll, Andrew M. Prentice, Brian F. Meyer, Ewan R. Pearson, Colin A.G. Boreham, Cyrus Cooper, Matthew W. Gillman, George V. Dedoussis, Luis A. Moreno, Oluf Pedersen, Maiju Saarinen, Karen L. Mohlke, Dorret I. Boomsma, Seang Mei Saw, Timo A. Lakka, Antje Körner, Ruth J.F. Loos, Ken K. Ong, Peter Vollenweider, Cornelia M. Van Duijn, Gerard H. Koppelman, Andrew T. Hattersley, John W. Holloway, Berthold Hocher, Joachim Heinrich, Chris Power, Mads Melbye, Mònica Guxens, Craig E. Pennell, Klaus Bønnelykke, Hans Bisgaard, Johan G. Eriksson, Elisabeth Widén, Hakon Hakonarson, André G. Uitterlinden, Anneli Pouta, Debbie A. Lawlor, George Davey Smith, Timothy M. Frayling, Mark I. McCarthy, Struan F.A. Grant, Vincent W.V. Jaddoe, Marjo Riitta Jarvelin, Nicholas J. Timpson, Inga Prokopenko, Rachel M. Freathy

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Abstract

Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.

Original languageEnglish
Pages (from-to)76-82
Number of pages7
JournalNature Genetics
Volume45
Issue number1
DOIs
Publication statusPublished - Jan 2013
Externally publishedYes

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ASJC Scopus subject areas

  • Genetics

Cite this

Horikoshi, M., Yaghootkar, H., Mook-Kanamori, D. O., Sovio, U., Taal, H. R., Hennig, B. J., Bradfield, J. P., St Pourcain, B., Evans, D. M., Charoen, P., Kaakinen, M., Cousminer, D. L., Lehtimäki, T., Kreiner-Møller, E., Warrington, N. M., Bustamante, M., Feenstra, B., Berry, D. J., Thiering, E., ... Freathy, R. M. (2013). New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism. Nature Genetics, 45(1), 76-82. https://doi.org/10.1038/ng.2477