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 Pfab, Sheila 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 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

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.