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
39159
2015
2015
eng
1155
1168
14
4
24
article
Oxford Univ. Press
Oxford
Early Genetics Lifecourse, Genetic Invest ANthropometric, Early Growth Genetics EGG
1
--
--
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A novel common variant in DCST2 is associated with length in early life and height in adulthood
Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N = 28 459). We identified seven independent top single nucleotide polymorphisms (SNPs) (P < 1 x 10(-6)) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The three novel SNPs were followed-up in nine replication studies (Stage 2; N = 11 995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1 + 2; beta = 0.046, SE = 0.008, P = 2.46 x 10(-8), explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 x 10(-4)) and adult height (N = 127 513; P = 1.45 x 10(-5)). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height.
Human molecular genetics
10.1093/hmg/ddu510
25281659
0964-6906
1460-2083
wos:2015
WOS:000350138300021
Jaddoe, VWV (reprint author), Sophias Childrens Hosp, Erasmus Med Ctr, Dept Epidemiol, Generat Study Grp R, Postbus 2060, NL-3000 CB Rotterdam, Netherlands., v.jaddoe@erasmusmc.nl
Sir Henry Wellcome Postdoctoral Fellowship (Wellcome Trust)
[085541/Z/08/Z]; Danish Council for Independent Research Medical
Sciences (FSS) The Alfred Benzon Foundation; Oak Foundation fellowship;
Wellcome Trust [090532]; European Research Council [SZ-245
50371-GLUCOSEGENES-FP7-IDEAS-ERC]; Netherlands Organization for Health
Research and Development [VIDI 016.136.367, VIDI 016.136.361]
Ralf J. P. van der Valk
Eskil Kreiner-Moller
Marjolein N. Kooijman
Monica Guxens
Evangelia Stergiakouli
Annika Saaf
Jonathan P. Bradfield
Frank Geller
M. Geoffrey Hayes
Diana L. Cousminer
Antje Koerner
Elisabeth Thiering
John A. Curtin
Ronny Myhre
Ville Huikari
Raimo Joro
Marjan Kerkhof
Nicole M. Warrington
Niina Pitkanen
Ioanna Ntalla
Momoko Horikoshi
Riitta Veijola
Rachel M. Freathy
Yik-Ying Teo
Sheila J. Barton
David M. Evans
John P. Kemp
Beate St Pourcain
Susan M. Ring
George Davey Smith
Anna Bergstrom
Inger Kull
Hakon Hakonarson
Frank D. Mentch
Hans Bisgaard
Bo Lund Krogsgaard Chawes
Jakob Stokholm
Johannes Waage
Patrick Eriksen
Astrid Sevelsted
Mads Melbye
Cornelia M. van Duijn
Carolina Medina-Gomez
Albert Hofman
Johan C. de Jongste
H. Rob Taal
Andre G. Uitterlinden
Loren L. Armstrong
Johan Eriksson
Aarno Palotie
Mariona Bustamante
Xavier Estivill
Juan R. Gonzalez
Sabrina Llop
Wieland Kiess
Anubha Mahajan
Claudia Flexeder
Carla M. T. Tiesler
Clare S. Murray
Angela Simpson
Per Magnus
Verena Sengpiel
Anna-Liisa Hartikainen
Sirkka Keinanen-Kiukaanniemi
Alexandra Lewin
Alexessander Da Silva Couto Alves
Alexandra I. F. Blakemore
Jessica L. Buxton
Marika Kaakinen
Alina Rodriguez
Sylvain Sebert
Marja Vaarasmaki
Timo Lakka
Virpi Lindi
Ulrike Gehring
Dirkje S. Postma
Wei Ang
John P. Newnham
Leo-Pekka Lyytikainen
Katja Pahkala
Olli T. Raitakari
Kalliope Panoutsopoulou
Eleftheria Zeggini
Dorret I. Boomsma
Maria Groen-Blokhuis
Jorma Ilonen
Lude Franke
Joel N. Hirschhorn
Tune H. Pers
Liming Liang
Jinyan Huang
Berthold Hocher
Mikael Knip
Seang-Mei Saw
John W. Holloway
Erik Melen
Struan F. A. Grant
Bjarke Feenstra
William L. Lowe
Elisabeth Widen
Elena Sergeyev
Harald Grallert
Adnan Custovic
Bo Jacobsson
Marjo-Riitta Jarvelin
Mustafa Atalay
Gerard H. Koppelman
Craig E. Pennell
Harri Niinikoski
George V. Dedoussis
Mark I. Mccarthy
Timothy M. Frayling
Jordi Sunyer
Nicholas J. Timpson
Fernando Rivadeneira
Klaus Bonnelykke
Vincent W. V. Jaddoe
Institut für Ernährungswissenschaft
Referiert