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
53521
2018
2018
eng
742
756
15
4
27
article
Oxford Univ. Press
Oxford
Early Growth Genetics EGG
1
2018-01-03
2018-01-03
--
Genome-wide association study of offspring birth weight in 86 577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics
Genome-wide association studies of birth weight have focused on fetal genetics, whereas relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86 577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother-child pairs to quantify the separate maternal and fetal genetic effects. Maternal SNPs at 10 loci (MTNR1B, HMGA2, SH2B3, KCNAB1, L3MBTL3, GCK, EBF1, TCF7L2, ACTL9, CYP3A7) were associated with offspring birth weight at P< 5 x 10(-8). In SEM analyses, at least 7 of the 10 associations were consistent with effects of the maternal genotype acting via the intrauterine environment, rather than via effects of shared alleles with the fetus. Variants, or correlated proxies, at many of the loci had been previously associated with adult traits, including fasting glucose (MTNR1B, GCK and TCF7L2) and sex hormone levels (CYP3A7), and one (EBF1) with gestational duration. The identified associations indicate that genetic effects on maternal glucose, cytochrome P450 activity and gestational duration, and potentially on maternal blood pressure and immune function, are relevant for fetal growth. Further characterization of these associations in mechanistic and causal analyses will enhance understanding of the potentially modifiable maternal determinants of fetal growth, with the goal of reducing the morbidity and mortality associated with low and high birth weights.
Human molecular genetics
10.1093/hmg/ddx429
29309628
0964-6906
1460-2083
wos:2018
WOS:000424137500014
Lawlor, DA (reprint author), Univ Bristol, Med Res Council Integrat Epidemiol Unit, Oakfield House,Oakfield Rd, Bristol BS8 2BN, Avon, England.; Freathy, RM (reprint author), Univ Exeter, Royal Devon & Exeter Hosp, Med Sch, RILD Bldg, Exeter EX2 5DW, Devon, England.; Feenstra, B (reprint author), Statens Serum Inst, Dept Epidemiol Res, Artillerivej 5, DK-2300 Copenhagen S, Denmark.; Evans, DM (reprint author), Univ Queensland, Diamantina Inst, Brisbane, Qld, Australia., d.evans1@uq.edu.au; d.a.lawlor@bristol.ac.uk; fee@ssi.dk; r.freathy@ex.ac.uk
European Regional Development Fund (ERDF)European Union (EU); European Social Fund (ESF) Convergence Programme for Cornwall and the Isles of Scilly; European Research Council (ERC)European Research Council (ERC) [SZ-245 50371-GLUCOSEGENES-FP7-IDEAS-ERC, ERC-2014-CoG-648916]; University of Bergen, KG Jebsen; University of Bergen, Helse Vest; Wellcome Trust Senior Investigator AwardsWellcome Trust [WT098395, WT098381]; National Institute for Health Research (NIHR) Senior Investigator AwardNational Institute for Health Research (NIHR) [NF-SI-0611-10219]; Sir Henry Dale Fellowship (Wellcome Trust); Sir Henry Dale Fellowship (Royal Society grant) [WT104150]; 4-year studentship [WT083431MF]; European Research Council under the European US National Institute of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01 DK10324]; Wellcome Trust GWAS grantWellcome Trust [WT088806]; NIHR Senior Investigator Award [NF-SI-0611-10196]; Wellcome Trust Institutional Strategic Support AwardWellcome Trust [WT097835MF]; Diabetes Research and Wellness Foundation Non-Clinical Fellowship; Australian National Health and Medical Research Council Early Career FellowshipNational Health and Medical Research Council of Australia [APP1104818]; Daniel B. Burke Endowed Chair for Diabetes Research; UK Medical Research Council Unit grants [MC_UU_12013_5, MC_UU_12013_4]; Medical Research CouncilMedical Research Council UK (MRC) [MR/M005070/1]; Australian Research Council Future FellowshipAustralian Research Council [FT130101709, FT110100548]; NIHR Oxford Biomedical Research Centre (BRC); Oak Foundation Fellowship; Novo Nordisk FoundationNovo Nordisk Foundation [12955]; Canadian Diabetes Association; Institute of Genetics-Canadian Institute of Health Research (CIHR); CIHR-Frederick Banting and Charles Best Canada Graduate ScholarshipsCanadian Institutes of Health Research (CIHR); FRQS; Netherlands Organization for Health Research and DevelopmentNetherlands Organization for Health Research and Development [ZonMw-VIDI 016.136.361]; National Institute on AgingUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Aging (NIA) [R01AG29451]; PRIN funds of the University of Ferrara; European Foundation for the Study of Diabetes (EFSD) Albert Renold Travel Fellowships for Young Scientists; ENGAGE Exchange and Mobility Program for ENGAGE training funds, ENGAGE project [HEALTH-F4-2007-201413]; ESRCEconomic & Social Research Council (ESRC) [RES-060-23-0011]; National Institute of Health ResearchNational Institute for Health Research (NIHR); Australian NHMRC Fellowships SchemeNational Health and Medical Research Council of Australia [619667]; Charity Open Access Fund (COAF)
2022-01-19T14:02:29+00:00
sword
importub
filename=package.tar
028f265f4fe9c904a10e512801030635
<a href="https://doi.org/10.25932/publishup-42310">Zweitveröffentlichung in der Schriftenreihe Postprints der Universität Potsdam : Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe ; 628 </a>
false
true
Robin N. Beaumont
Nicole M. Warrington
Alana Cavadino
Jessica Tyrrell
Michael Nodzenski
Momoko Horikoshi
Frank Geller
Ronny Myhre
Rebecca C. Richmond
Lavinia Paternoster
Jonathan P. Bradfield
Eskil Kreiner-Moller
Ville Huikari
Sarah Metrustry
Kathryn L. Lunetta
Jodie N. Painter
Jouke-Jan Hottenga
Catherine Allard
Sheila J. Barton
Ana Espinosa
Julie A. Marsh
Catherine Potter
Ge Zhang
Wei Ang
Diane J. Berry
Luigi Bouchard
Shikta Das
Hakon Hakonarson
Jani Heikkinen
Oyvind Helgeland
Berthold Hocher
Albert Hofman
Hazel M. Inskip
Samuel E. Jones
Manolis Kogevinas
Penelope A. Lind
Letizia Marullo
Sarah E. Medland
Anna Murray
Jeffrey C. Murray
Pal R. Njolstad
Ellen A. Nohr
Christoph Reichetzeder
Susan M. Ring
Katherine S. Ruth
Loreto Santa-Marina
Denise M. Scholtens
Sylvain Sebert
Verena Sengpiel
Marcus A. Tuke
Marc Vaudel
Michael N. Weedon
Gonneke Willemsen
Andrew R. Wood
Hanieh Yaghootkar
Louis J. Muglia
Meike Bartels
Caroline L. Relton
Craig E. Pennell
Leda Chatzi
Xavier Estivill
John W. Holloway
Dorret I. Boomsma
Grant W. Montgomery
Joanne M. Murabito
Tim D. Spector
Christine Power
Marjo-Ritta Jarvelin
Hans Bisgaard
Struan F. A. Grant
Thorkild I. A. Sorensen
Vincent W. Jaddoe
Bo Jacobsson
Mads Melbye
Mark I. McCarthy
Andrew T. Hattersley
M. Geoffrey Hayes
Timothy M. Frayling
Marie-France Hivert
Janine F. Felix
Elina Hypponen
William L. Lowe
David M. Evans
Debbie A. Lawlor
Bjarke Feenstra
Rachel M. Freathy
Biowissenschaften; Biologie
Institut für Biochemie und Biologie
Referiert
Import
Hybrid Open-Access
42310
2017
2019
eng
15
628
postprint
1
2019-02-20
2019-02-20
--
Genome-wide association study of offspring birth weight in 86 577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics
Genome-wide association studies of birth weight have focused on fetal genetics, whereas relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86 577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother–child pairs to quantify the separate maternal and fetal genetic effects. Maternal SNPs at 10 loci (MTNR1B, HMGA2, SH2B3, KCNAB1, L3MBTL3, GCK, EBF1, TCF7L2, ACTL9, CYP3A7) were associated with offspring birth weight at P < 5 Â 10 À8 . In SEM analyses, at least 7 of the 10 associations were consistent with effects of the maternal genotype acting via the intrauterine environment, rather than via effects of shared alleles with the fetus. Variants, or correlated proxies, at many of the loci had been previously associated with adult traits, including fasting glucose (MTNR1B, GCK and TCF7L2) and sex hormone levels (CYP3A7), and one (EBF1) with gestational duration. The identified associations indicate that genetic effects on maternal glucose, cytochrome P450 activity and gestational duration, and potentially on maternal blood pressure and immune function, are relevant for fetal growth. Further characterization of these associations in mechanistic and causal analyses will enhance understanding of the potentially modifiable maternal determinants of fetal growth, with the goal of reducing the morbidity and mortality associated with low and high birth weights.
Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe
10.25932/publishup-42310
urn:nbn:de:kobv:517-opus4-423100
1866-8372
online registration
Human Molecular Genetics 27 (2018) 4, pp. 742–756 DOI 10.1093/hmg/ddx429
<a href="http://publishup.uni-potsdam.de/53521">Bibliographieeintrag der Originalveröffentlichung/Quelle</a>
CC-BY - Namensnennung 4.0 International
Robin N. Beaumont
Nicole M. Warrington
Alana Cavadino
Jessica Tyrrell
Michael Nodzenski
Momoko Horikoshi
Frank Geller
Ronny Myhre
Rebecca C. Richmond
Lavinia Paternoster
Jonathan P. Bradfield
Eskil Kreiner-Møller
Ville Huikari
Sarah Metrustry
Kathryn L. Lunetta
Jodie N. Painter
Jouke-Jan Hottenga
Catherine Allard
Sheila J. Barton
Ana Espinosa
Julie A. Marsh
Catherine Potter
Ge Zhang
Wei Ang
Diane J. Berry
Luigi Bouchard
Shikta Das
Hakon Hakonarson
Jani Heikkinen
Øyvind Helgeland
Berthold Hocher
Albert Hofman
Hazel M. Inskip
Samuel E. Jones
Manolis Kogevinas
Penelope A. Lind
Letizia Marullo
Sarah E. Medland
Anna Murray
Jeffrey C. Murray
Pa ̊l R. Njølstad
Ellen A. Nohr
Christoph Reichetzeder
Susan M. Ring
Katherine S. Ruth
Loreto Santa-Marina
Denise M. Scholtens
Sylvain Sebert
Verena Sengpiel
Marcus A. Tuke
Marc Vaudel
Michael N. Weedon
Gonneke Willemsen
Andrew R. Wood
Hanieh Yaghootkar
Louis J. Muglia
Meike Bartels
Caroline L. Relton
Craig E. Pennell
Leda Chatzi
Xavier Estivill
John W. Holloway
Dorret I. Boomsma
Grant W. Montgomery
Joanne M. Murabito
Tim D. Spector
Christine Power
Marjo-Ritta Ja ̈rvelin
Hans Bisgaard
Struan F.A. Grant
Thorkild I.A. Sørensen
Vincent W. Jaddoe
Bo Jacobsson
Mads Melbye
Mark I. McCarthy
Andrew T. Hattersley
M. Geoffrey Hayes
Timothy M. Frayling
Marie-France Hivert
Janine F. Felix
Elina Hyppo ̈nen
William L. , Jr Lowe
David M. Evans
Debbie A. Lawlor
Bjarke Feenstra
Rachel M. Freathy
Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe
628
eng
uncontrolled
alleles
eng
uncontrolled
birth weight
eng
uncontrolled
fetus
eng
uncontrolled
genotype
eng
uncontrolled
mothers
eng
uncontrolled
single nucleotide polymorphism
eng
uncontrolled
genetics
eng
uncontrolled
duration of gestation
eng
uncontrolled
genome-wide association study
eng
uncontrolled
offspring
eng
uncontrolled
biobanks
Biowissenschaften; Biologie
Tiere (Zoologie)
open_access
Mathematisch-Naturwissenschaftliche Fakultät
Referiert
Open Access
Universität Potsdam
https://publishup.uni-potsdam.de/files/42310/pmnr628.pdf