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

Authors:
Dr Zoltán Kutalik, PhD
Dr Zoltán Kutalik, PhD
Institute of Social and Preventive Medicine, CHUV
Assistant Professor
Biostatistics
Lausanne, Vaud | Switzerland
Dr Anubha Mahajan, PhD
Dr Anubha Mahajan, PhD
Wellcome Trust Centre for Human Genetics, University of Oxford
UK
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 Jing Hua Zhao Marcel den Hoed 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 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

Nat Genet 2013 Jan 2;45(1):76-82. Epub 2012 Dec 2.

Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.

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.

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http://dx.doi.org/10.1038/ng.2477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3605762PMC
January 2013
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