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

2012; Nature Portfolio; Volume: 45; Issue: 1 Linguagem: Inglês

10.1038/ng.2477

1546-1718

Momoko Horikoshi, Hanieh Yaghootkar, Dennis O. Mook‐Kanamori, Ulla Sovio, H. Rob Taal, Branwen J. Hennig, Jonathan P. Bradfield, Beaté 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 Pfab, Sheila J. Barton, Beverley M. Shields, Marjan Kerkhof, Jin‐Moo Lee, Anthony J. Fulford, Zoltán Kutalik, Wei Zhao, Marcel den Hoed, Anubha Mahajan, Virpi Lindi, Liang-Kee Goh, Jouke‐Jan Hottenga, Ying Wu, Olli T. Raitakari, Marie Neergaard Harder, Aline Meirhaeghe, Ιωάννα Ντάλλα, Rany M. Salem, Anthony James, Kaixin Zhou, Dorota Monies, Vasiliki Lagou, Mirna Kirin, Jani Heikkinen, Linda S. Adair, Fowzan S. Alkuraya, Ali Al‐Odaib, Philippe Amouyel, Ehm A. Andersson, Amanda J. Bennett, Alexandra I. F. Blakemore, Jessica L. Buxton, Jean Dallongeville, Shikta Das, Eco J. C. de Geus, Xavier Estivill, Claudia Flexeder, Philippe Froguel, Frank Geller, Keith M. Godfrey, F. Gottrand, Christopher J. Groves, Torben Hansen, Joel N. Hirschhorn, Albert Hofman, Mads V. Hollegaard, David M. Hougaard, Elina Hyppönen, Hazel Inskip, Aaron Isaacs, Torben Jørgensen, Christina Kanaka‐Gantenbein, John P. Kemp, Wieland Kieß, Tuomas O. Kilpeläinen, Norman Klopp, Bridget Knight, Christopher W. Kuzawa, George McMahon, John P. Newnham, Harri Niinikoski, Ben A. Oostra, Oluf Pedersen, Dirkje S. Postma, Susan M. Ring, Fernando Rivadeneira, Neil R. Robertson, Sylvain Sebért, Olli Simell, Torsten Slowinski, Carla M. T. Tiesler, Anke Tönjes, Allan Vaag, Jorma Viikari, Jacqueline M. Vink, Nadja Hawwa Vissing, Nicholas J. Wareham, Gonneke Willemsen, Daniel R. Witte, Haitao Zhang, Jianhua Zhao,

Epigenetics and DNA Methylation

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.