Variants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight

Rachel M. Freathy; Dennis O. Mook-Kanamori; Ulla Sovio; Inga Prokopenko; Nicholas J. Timpson; Diane J. Berry; Nicole M. Warrington; Elisabeth Widen; Jouke Jan Hottenga; Marika Kaakinen; Leslie A. Lange; Jonathan P. Bradfield; Marjan Kerkhof; Julie A. Marsh; Reedik Maegi; Chih-Mei Chen; Helen N. Lyon; Mirna Kirin; Linda S. Adair; Yurii S. Aulchenko; Amanda J. Bennett; Judith B. Borja; Nabila Bouatia-Naji; Pimphen Charoen; Lachlan J. M. Coin; Diana L. Cousminer; Eco J. C. de Geus; Panos Deloukas; Paul Elliott; David M. Evans; Philippe Froguel; Beate Glaser; Christopher J. Groves; Anna-Liisa Hartikainen; Neelam Hassanali; Joel N. Hirschhorn; Albert Hofman; Jeff M. P. Holly; Elina Hyppoenen; Stavroula Kanoni; Bridget A. Knight; Jaana Laitinen; Cecilia M. Lindgren; Wendy L. McArdle; Paul F. O'Reilly; Craig E. Pennell; Dirkje S. Postma; Anneli Pouta; Adaikalavan Ramasamy; Nigel W. Rayner; Susan M. Ring; Fernando Rivadeneira; Beverley M. Shields; David P. Strachan; Ida Surakka; Anja Taanila; Carla Tiesler; Andre G. Uitterlinden; Cornelia M. van Duijn; Alet H. Wijga; Gonneke Willemsen; Haitao Zhang; Jianhua Zhao; James F. Wilson; Eric A. P. Steegers; Andrew T. Hattersley; Johan G. Eriksson; Leena Peltonen; Karen L. Mohlke; Struan F. A. Grant; Hakon Hakonarson; Gerard H. Koppelman; George V. Dedoussis; Joachim Heinrich; Matthew W. Gillman; Lyle J. Palmer; Timothy M. Frayling; Dorret I. Boomsma; George Davey Smith; Chris Power; Vincent W. V. Jaddoe; Marjo-Riitta Jarvelin; Mark I. McCarthy; EGG Consortium

doi:10.1038/ng.567

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Variants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight

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Variants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight

Rachel M. Freathy, Dennis O. Mook-Kanamori, Ulla Sovio, Inga Prokopenko, Nicholas J. Timpson, Diane J. Berry, Nicole M. Warrington, Elisabeth Widen, Jouke Jan Hottenga, Marika Kaakinen, …

Nature genetics, Vol.42(5), pp.430-U73

01/05/2010

DOI: https://doi.org/10.1038/ng.567

PMID: 20372150

Abstract

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

To identify genetic variants associated with birth weight, we meta-analyzed six genome-wide association (GWA) studies (n = 10,623 Europeans from pregnancy/birth cohorts) and followed up two lead signals in 13 replication studies (n = 27,591). rs900400 near LEKR1 and CCNL1 (P = 2 x 10(-35)) and rs9883204 in ADCY5 (P = 7 x 10(-15)) were robustly associated with birth weight. Correlated SNPs in ADCY5 were recently implicated in regulation of glucose levels and susceptibility to type 2 diabetes(1), providing evidence that the well-described association between lower birth weight and subsequent type 2 diabetes(2,3) has a genetic component, distinct from the proposed role of programming by maternal nutrition. Using data from both SNPs, we found that the 9% of Europeans carrying four birth weight-lowering alleles were, on average, 113 g (95% CI 89-137 g) lighter at birth than the 24% with zero or one alleles (P-trend = 7 x 10(-30)). The impact on birth weight is similar to that of a mother smoking 4-5 cigarettes per day in the third trimester of pregnancy(4).

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Title: Variants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight
Creators: Rachel M. Freathy - University of Exeter
Dennis O. Mook-Kanamori - Erasmus MC
Ulla Sovio - University of London
Inga Prokopenko - University of Oxford
Nicholas J. Timpson - University of Bristol
Diane J. Berry - Biostat
Nicole M. Warrington - Univ Western Australia, Ctr Genet Epidemiol & Biostat, Perth, WA 6009, Australia
Elisabeth Widen - University of Helsinki
Jouke Jan Hottenga - University of Amsterdam
Marika Kaakinen - University of Oulu
Leslie A. Lange - Univ N Carolina, Dept Genet, Chapel Hill, NC USA
Jonathan P. Bradfield - Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA USA
Marjan Kerkhof - University of Groningen
Julie A. Marsh - Univ Western Australia, Ctr Genet Epidemiol & Biostat, Perth, WA 6009, Australia
Reedik Maegi - University of Oxford
Chih-Mei Chen - German Res Ctr Environm Hlth, Helmholtz Zentrum Muenchen, Inst Epidemiol, Neuherberg, Germany
Helen N. Lyon - Childrens Hosp, Program Genom, Div Genet, Boston, MA 02115 USA
Mirna Kirin - University of Edinburgh
Linda S. Adair - Univ N Carolina, Dept Nutr, Chapel Hill, NC USA
Yurii S. Aulchenko - Erasmus MC
Amanda J. Bennett - University of Oxford
Judith B. Borja - University of San Carlos
Nabila Bouatia-Naji - Queen Saovabha Memorial Institute
Pimphen Charoen - University of London
Lachlan J. M. Coin - University of London
Diana L. Cousminer - University of Helsinki
Eco J. C. de Geus - University of Amsterdam
Panos Deloukas - Wellcome Sanger Institute
Paul Elliott - University of London
David M. Evans - University of Bristol
Philippe Froguel - Queen Saovabha Memorial Institute
Beate Glaser - University of Bristol
Christopher J. Groves - University of Oxford
Anna-Liisa Hartikainen - University of Oulu
Neelam Hassanali - University of Oxford
Joel N. Hirschhorn - Childrens Hosp, Program Genom, Div Genet, Boston, MA 02115 USA
Albert Hofman - Erasmus MC
Jeff M. P. Holly - University of Bristol
Elina Hyppoenen - Biostat
Stavroula Kanoni - Harokopio University of Athens
Bridget A. Knight - University of Exeter
Jaana Laitinen - Oulu Reg Inst Occupat Hlth, Oulu, Finland
Cecilia M. Lindgren - University of Oxford
Wendy L. McArdle - University of Bristol
Paul F. O'Reilly - University of London
Craig E. Pennell
Dirkje S. Postma - Univ Western Australia, Sch Womens & Infants Hlth, Perth, WA 6009, Australia
Anneli Pouta - Natl Inst Hlth & Welf, Oulu, Finland
Adaikalavan Ramasamy - University of London
Nigel W. Rayner - University of Oxford
Susan M. Ring - University of Bristol
Fernando Rivadeneira - Erasmus MC
Beverley M. Shields - University of Exeter
David P. Strachan - University of London
Ida Surakka - University of Helsinki
Anja Taanila - University of Oulu
Carla Tiesler - German Res Ctr Environm Hlth, Helmholtz Zentrum Muenchen, Inst Epidemiol, Neuherberg, Germany
Andre G. Uitterlinden - Erasmus MC
Cornelia M. van Duijn - Erasmus MC
Alet H. Wijga - Natl Inst Publ Hlth & Environm RIVM, Ctr Prevent & Hlth Serv Res, Bilthoven, Netherlands
Gonneke Willemsen - University of Amsterdam
Haitao Zhang - Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA USA
Jianhua Zhao - Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA USA
James F. Wilson - University of Edinburgh
Eric A. P. Steegers - Erasmus MC
Andrew T. Hattersley - University of Exeter
Johan G. Eriksson - University of Helsinki
Leena Peltonen - University of Helsinki
Karen L. Mohlke - Univ N Carolina, Dept Genet, Chapel Hill, NC USA
Struan F. A. Grant - Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA USA
Hakon Hakonarson - Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA USA
Gerard H. Koppelman - University of Groningen
George V. Dedoussis - Harokopio University of Athens
Joachim Heinrich - German Res Ctr Environm Hlth, Helmholtz Zentrum Muenchen, Inst Epidemiol, Neuherberg, Germany
Matthew W. Gillman - Harvard University
Lyle J. Palmer - Univ Western Australia, Ctr Genet Epidemiol & Biostat, Perth, WA 6009, Australia
Timothy M. Frayling
Dorret I. Boomsma - University of Amsterdam
George Davey Smith - University of Bristol
Chris Power - Biostat
Vincent W. V. Jaddoe - Erasmus MC
Marjo-Riitta Jarvelin - University of London
Mark I. McCarthy - University of Oxford
EGG Consortium
Publication Details: Nature genetics, Vol.42(5), pp.430-U73
Publisher: NATURE PORTFOLIO
Number of pages: 8
Date published: 01/05/2010
Grant note: 085301; 068545/Z/02; 076113/B/04/Z; 085541/Z/08/Z; 89061/Z/09/Z / Wellcome Trust 08/0003692 / Diabetes UK Children's Hospital of Philadelphia British Heart Foundation Exeter National Health Service Research and Development PHCS/C4/4/016 / National Institute for Health Research; National Institutes of Health Research (NIHR) Center for Medical Systems Biology Healthway Western Australia Institut fur Umweltmedizinische Forschung (IUF) Dusseldorf UK Department of Health Policy Research Programme
Identifiers: 99928955102346
Academic Unit: School of Biosciences
Language: English
Resource Type: Journal article

Variants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight

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