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; +140 more... 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 IF Blakemore; Jessica L Buxton; Jean Dallongeville; Shikta Das; Eco JC 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 MT 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; Meta-Analyses of Glucose- and Insulin-related traits Consortium ; James F Wilson; Michael Stumvoll; Andrew M Prentice

; Brian F Meyer; Ewan R Pearson; Colin AG 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 JF 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 FA Grant; Vincent WV Jaddoe; Marjo-Riitta Jarvelin; Nicholas J Timpson; Inga Prokopenko; Rachel M Freathy; Early Growth Genetics (EGG) Consortium; (2013) New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism. Nature genetics, 45 (1). pp. 76-82. ISSN 1061-4036 DOI: 10.1038/ng.2477

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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.