49661
2019
2019
eng
804
+
17
5
51
article
Nature Publ. Group
New York
EGG Consortium
1
2019-05-01
2019-05-01
--
Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors
Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.
Nature genetics
31043758
1061-4036
1546-1718
wos:2019
WOS:000466842000008
Evans, DM (reprint author), Univ Queensland, Translat Res Inst, Diamantina Inst, Brisbane, Qld, Australia.; Freathy, RM (reprint author), Univ Exeter, Inst Biomed & Clin Sci, Royal Devon & Exeter Hosp, Coll Med & Hlth, Exeter, Devon, England.; Evans, DM; Freathy, RM (reprint author), Univ Bristol, Med Res Council, Integrat Epidemiol Unit, Bristol, Avon, England.; Evans, DM (reprint author), Univ Bristol, Bristol Med Sch, Populat Hlth Sci, Bristol, Avon, England., d.evans1@uq.edu.au; r.freathy@ex.ac.uk
Diabetes UKDiabetes UK [17/0005594]; European Research CouncilEuropean Research Council (ERC) [323195]; Medical Research CouncilMedical Research Council UK (MRC) [MC_PC_15018, MC_UU_12011/4, MC_UU_00011/6, MC_UU_12013/4, MR/M005070/1, MR/J012165/1, MC_UU_00011/1, G9815508, G0601261, MC_UU_00011/5, MC_UP_A620_1017, MC_UU_12015/1, MC_UU_12013/3, G1001357]; NIEHS NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Environmental Health Sciences (NIEHS) [R01 ES022223, R21 ES028226, R24 ES028507, P30 ES019776, P30 ES023515, R01 ES029212]; Wellcome TrustWellcome Trust [202802, 104150, 098395, 205915, 098381, 212259, 088806]
2021-02-25T12:53:57+00:00
sword
importub
filename=package.tar
84117ccb625356b05295ebe98606c698
Evans, David M.
Freathy, Rachel M.
Nicole Warrington
Robin Beaumont
Momoko Horikoshi
Felix R. Day
Øyvind Helgeland
Charles Laurin
Jonas Bacelis
Shouneng Peng
Ke Hao
Bjarke Feenstra
Andrew R. Wood
Anubha Mahajan
Jessica Tyrrell
Neil R. Robertson
N. William Rayner
Zhen Qiao
Gunn-Helen Moen
Marc Vaudel
Carmen Marsit
Jia Chen
Michael Nodzenski
Theresia M. Schnurr
Mohammad Hadi Zafarmand
Jonathan P. Bradfield
Niels Grarup
Marjolein N. Kooijman
Ruifang Li-Gao
Frank Geller
Tarunveer Singh Ahluwalia
Lavinia Paternoster
Rico Rueedi
Ville Huikari
Jouke-Jan Hottenga
Leo-Pekka Lyytikäinen
Alana Cavadino
Sarah Metrustry
Diana L. Cousminer
Ying Wu
Elisabeth Paula Thiering
Carol A. Wang
Christian Theil Have
Natalia Vilor-Tejedor
Peter K. Joshi
Jodie N. Painter
Ioanna Ntalla
Ronny Myhre
Niina Pitkänen
Elisabeth M. van Leeuwen
Raimo Joro
Vasiliki Lagou
Rebecca C. Richmond
Ana Espinosa
Sheila J. Barton
Hazel M. Inskip
John W. Holloway
Loreto Santa-Marina
Xavier Estivill
Wei Ang
Julie A. Marsh
Christoph Reichetzeder
Letizia Marullo
Berthold Hocher
Kathryn L. Lunetta
Joanne M. Murabito
Caroline L. Relton
Manolis Kogevinas
Leda Chatzi
Catherine Allard
Luigi Bouchard
Marie-France Hivert
Ge Zhang
Louis J. Muglia
Jani Heikkinen
Camilla S. Morgen
Antoine H. C. van Kampen
Barbera D. C. van Schaik
Frank D. Mentch
Claudia Langenberg
Robert A. Scott
Jing Hua Zhao
Gibran Hemani
Susan M. Ring
Amanda J. Bennett
Kyle J. Gaulton
Juan Fernandez-Tajes
Natalie R. van Zuydam
Carolina Medina-Gomez
Hugoline G. de Haan
Frits R. Rosendaal
Zoltán Kutalik
Pedro Marques-Vidal
Shikta Das
Gonneke Willemsen
Hamdi Mbarek
Martina Müller-Nurasyid
Marie Standl
Emil V. R. Appel
Cilius Esmann Fonvig
Caecilie Trier
Catharina E. M. van Beijsterveldt
Mario Murcia
Mariona Bustamante
Sílvia Bonàs-Guarch
David M. Hougaard
Josep M. Mercader
Allan Linneberg
Katharina E. Schraut
Penelope A. Lind
Sarah Elizabeth Medland
Beverley M. Shields
Bridget A. Knight
Jin-Fang Chai
Kalliope Panoutsopoulou
Meike Bartels
Friman Sánchez
Jakob Stokholm
David Torrents
Rebecca K. Vinding
Sara M. Willems
Mustafa Atalay
Bo L. Chawes
Peter Kovacs
Inga Prokopenko
Marcus A. Tuke
Hanieh Yaghootkar
Katherine S. Ruth
Samuel E. Jones
Po-Ru Loh
Anna Murray
Michael N. Weedon
Anke Tönjes
Michael Stumvoll
Kim Fleischer Michaelsen
Aino-Maija Eloranta
Timo A. Lakka
Cornelia M. van Duijn
Wieland Kiess
Antje Koerner
Harri Niinikoski
Katja Pahkala
Olli T. Raitakari
Bo Jacobsson
Eleftheria Zeggini
George V. Dedoussis
Yik-Ying Teo
Seang-Mei Saw
Grant W. Montgomery
Harry Campbell
James F. Wilson
Tanja G. M. Vrijkotte
Martine Vrijheid
Eco J. C. N. de Geus
M. Geoffrey Hayes
Haja N. Kadarmideen
Jens-Christian Holm
Lawrence J. Beilin
Craig E. Pennell
Joachim Heinrich
Linda S. Adair
Judith B. Borja
Karen L. Mohlke
Johan G. Eriksson
Elisabeth E. Widen
Andrew T. Hattersley
Tim D. Spector
Mika Kaehoenen
Jorma S. Viikari
Terho Lehtimaeki
Dorret I. Boomsma
Sylvain Sebert
Peter Vollenweider
Thorkild I. A. Sorensen
Hans Bisgaard
Klaus Bonnelykke
Jeffrey C. Murray
Mads Melbye
Ellen A. Nohr
Dennis O. Mook-Kanamori
Fernando Rivadeneira
Albert Hofman
Janine F. Felix
Vincent W. V. Jaddoe
Torben Hansen
Charlotta Pisinger
Allan A. Vaag
Oluf Pedersen
Andre G. Uitterlinden
Marjo-Riitta Jarvelin
Christine Power
Elina Hypponen
Denise M. Scholtens
William L. Lowe
George Davey Smith
Nicholas J. Timpson
Andrew P. Morris
Nicholas J. Wareham
Hakon Hakonarson
Struan F. A. Grant
Timothy M. Frayling
Debbie A. Lawlor
Pal R. Njolstad
Stefan Johansson
Ken K. Ong
Mark I. McCarthy
John R. B. Perry
David M. Evans
Rachel M. Freathy
Institut für Ernährungswissenschaft
Referiert
Import
Green Open-Access
35420
2013
2013
eng
76
U115
10
1
45
article
Nature Publ. Group
New York
MAGIC, Early Growth Genetics EGG
1
--
--
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New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism
Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood(1). 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(2). In an expanded genome-wide association metaanalysis 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.
Nature genetics
10.1038/ng.2477
1061-4036
wos:2011-2013
WOS:000312838800016
McCarthy, MI (reprint author), Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England., mark.mccarthy@drl.ox.ac.uk; grants@chop.edu; v.jaddoe@erasmusmc.nl; m.jarvelin@imperial.ac.uk; n.j.timpson@bristol.ac.uk; ingap@well.ox.ac.uk; rachel.freathy@pms.ac.uk
Academy of Finland [126925, 121584, 124282, 129378, 117787, 41071,
209072, 129255, 104781, 120315, 129269, 1114194, 206374, 251360,
139900/24300796]; Biocentrum Helsinki; Arthritis Research UK; Augustinus
Foundation; Biobanking and Biomolecular Resources Research
Infrastructure (BBMRI-NL); Biomedical Research Council, Singapore [BMRC
06/1/21/19/466]; BIF: Boehringer Ingelheim Fonds; British Heart
Foundation; C.G. Sundell Foundation; Canadian Institutes of Health
Research [MOP-82893]; Cancer Research UK; Chief Scientist Office of the
Scottish Government; Children's Hospital of Philadelphia (Institute
Development Award); Conselleria de Sanitat Generalitat Valenciana;
Copenhagen Graduate School of Health Sciences; Cotswold Foundation
(Research Development Award); Curtin University and Women and Infants
Research Foundation; Danish Health Insurance Societies (Health Fund);
Danish Medical Research Council; Danish National Research Foundation;
Danish Pediatric Asthma Centre; Danish Pharmacists' Fund; Danish
Strategic Research Council; Darlington Trust; Department of Health and
Social Services in Northern Ireland; Deutsche Forschungsgemeinschaft
(DFG); Diabetes Hilfs-und Forschungsfonds Deutschland (DHFD); Diabetes
UK [RD08/0003704, RD08/0003692]; Dunhill Medical Trust; Dutch Asthma
Foundation [3.4.01.26, 3.2.06.022, 3.4.09.081, 3.2.10.085CO]; Dutch
Ministry of the Environment (EFRE); Europaische Fonds fur Regionale
Entwicklung (LIFE Child Obesity); Egmont Foundation; Else
Kroner-Fresenius Foundation; Emil Aaltonen Foundation; ENGAGE project
[HEALTH-F4-2007-201413]; Erasmus Medical Center; Erasmus University,
Rotterdam; European Commission [QLG1-CT-2000-01643, 018996,
LSHG-CT-2006-018947, FOOD-CT-2005-007034]; European Research Council
(ERC Advanced) [230374]; European Science Foundation (ESF)
[EU/QLRT-2001-01254]; Exeter NHS Research and Development; Faculty of
Biology and Medicine of Lausanne; Finnish Foundation of Cardiovascular
Research; Finnish Cultural Foundation; Finnish Innovation Fund Sitra;
Finnish Ministry of Education and Culture; Finnish Ministry of Social
Affairs and Health; Finnish Social Insurance Institution; Foundation for
Paediatric Research; Fundacio La Marato de TV3; Fundacion Roger Torne;
Generalitat de Catalunya-Interminesterial Council for Research and
Technological Innovation (CIRIT) [(1999SGR) 00241]; German Diabetes
Association; German Bundesministerium fuer Forschung und Technology [01
AK 803 A-H, 01 IG 07015 G]; German Research Foundation for the Clinical
Research Group Atherobesity [KO3512/1]; GlaxoSmithKline; Hagedorn
Research Institute; Instituto de Salud Carlos III [CB06/02/0041, FIS
PI041436, PI081151, PI041705, PS09/00432, FISFEDER 03/1615, 04/1509,
04/1112, 04/1931, 05/1079, 05/1052, 06/1213, 07/0314, 09/02647];
Interdisciplinary Centre for Clinical Research at the University of
Leipzig [B27]; Integrated Research and Treatment Centre (IFB) Adiposity
Diseases; Jackstadt-Foundation; Juho Vainio Foundation; Juvenile
Diabetes Research Foundation International (JDRF); Kuopio, Tampere and
Turku University Hospital Medical Funds [5031343, 9M048]; Lundbeck
Foundation; Lundbeck Foundation Centre of Applied Medical Genomics for
Personalized Disease Prediction, Prevention and Care (LuCAMP); March of
Dimes Birth Defects Foundation [6-FY09-507]; MRC, UK [74882, G0000934,
G0601653, G0500539, G0600705, G0601261, G0600331, PrevMetSyn/SALVE
PS0476, MC-A760-5QX00]; Munich Center of Health Sciences (MC Health);
National Health and Medical Research Council of Australia [403981,
003209]; US National Human Genome Research Institute; US National
Institute of Allergy and Infectious Diseases; US National Institute of
Child Health and Human Development; US National Institute of Diabetes
and Digestive and Kidney Diseases (NIDDK); US National Institutes of
Health [U01DK062418, U01HG004423, U01HG004446, U01HG004438, R01DK075787,
1R01HD056465-01A, R01D0042157-01A, DK078150, TW05596, HL085144,
HD054501, RR20649, ES10126, DK56350]; Netherlands Bioinformatics Centre
(NBIC) BioAssist [RK/2008.024]; National Heart, Lung, and Blood
Institute (NHLBI) [5R01HL087679-02]; National Heart, Lung, and Blood
Institute (NHLBI) through the STAMPEED program [1RL1MH083268-01]; NIH
Genetic Association Information Network (GAIN); NIH/National Institute
of Mental Health (NIMH) [5R01MH63706: 02, MH081802]; Rutgers University
Cell and DNA Repository cooperative agreement [NIMH U24 MH068457-06];
Novo Nordisk Foundation Center for Basic Metabolic Research; Center for
Medical Systems Biology (CMSB; NWO Genomics); Netherlands Organization
for Scientific Research (NWO: Social Sciences (MaGW); Netherlands
Organization for Health Research and Development (ZonMw)
[Middelgroot-911-09-032, Spinozapremie 56-464-14192, 904-61-090,
904-61-193, 480-04-004, 400-05-717, Addiction-31160008, 985-10-002,
40-005698- 9032, 912-03-031]; Paavo Nurmi Foundation; Peninsula NIHR
Clinical Research Facility; Pharmacy Foundation of 1991; PhD School of
Molecular Metabolism University of Southern Denmark; Raine Medical
Research Foundation; Royal Society; Sigrid Juselius Foundation; South
West NHS Research and Development; Spanish Ministry of Science and
Innovation [SAF2008-00357]; Turku University Hospital; Swiss National
Science Foundation [33CSCO-122661]; Tampere Tuberculosis Foundation;
Telethon Institute for Child Health Research; Turku University
Foundation; US Centers for Disease Control and Prevention; University
Hospital Oulu, Biocenter, the University of Oulu [75617]; University of
Bristol; University of Potsdam; University of Southampton; University of
Western Australia (UWA); VU Institute for Health and Care Research
(EMGO+); Neuroscience Campus Amsterdam (NCA); Wellcome Trust [GR069224,
WT088806, 068545/Z/02, 076467, 085301, 090532, 083270, 083948,
085541/Z/08/Z, WT089549, WT083431MA]; Yrjo Jahnsson Foundation; Academy
of Finland (Center of Excellence in Complex Disease Genetics); Academy
of Finland (SALVE)
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 Lehtimaki
Eskil Kreiner-Moller
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
Zoltan 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
Frederic Gottrand
Christopher J. Groves
Torben Hansen
Joel N. Hirschhorn
Albert Hofman
Mads V. Hollegaard
David M. Hougaard
Elina Hyppoenen
Hazel M. Inskip
Aaron Isaacs
Torben Jorgensen
Christina Kanaka-Gantenbein
John P. Kemp
Wieland Kiess
Tuomas O. Kilpelainen
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 Toenjes
Allan Vaag
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Jacqueline M. Vink
Nadja Hawwa Vissing
Nicholas J. Wareham
Gonneke Willemsen
Daniel R. Witte
Haitao Zhang
Jianhua Zhao
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Ewan R. Pearson
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Cyrus Cooper
Matthew W. Gillman
George V. Dedoussis
Luis A. Moreno
Oluf Pedersen
Maiju Saarinen
Karen L. Mohlke
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Seang-Mei Saw
Timo A. Lakka
Antje Koerner
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
Monica Guxens
Craig E. Pennell
Klaus Bonnelykke
Hans Bisgaard
Johan G. Eriksson
Elisabeth Widen
Hakon Hakonarson
Andre 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
Institut für Ernährungswissenschaft
Referiert