Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors.

Warrington, N.M.; Beaumont, R.N.; Horikoshi, M.; Day, F.R.; Helgeland, Ø.; Laurin, C.; Bacelis, J.; Peng, S.; Hao, K.; Feenstra, B.; Wood, A.R.; Mahajan, A.; Tyrrell, J.; Robertson, N.R.; Rayner, N.W.; Qiao, Z.; Moen, G.H.; Vaudel, M.; Marsit, C.J.; Chen, J.; Nodzenski, M.; Schnurr, T.M.; Zafarmand, M.H.; Bradfield, J.P.; Grarup, N.; Kooijman, M.N.; Li-Gao, R.; Geller, F.; Ahluwalia, T.S.; Paternoster, L.; Rueedi, R.; Huikari, V.; Hottenga, J.J.; Lyytikäinen, L.P.; Cavadino, A.; Metrustry, S.; Cousminer, D.L.; Wu, Y.; Thiering, E.; Wang, C.A.; Have, C.T.; Vilor-Tejedor, N.; Joshi, P.K.; Painter, J.N.; Ntalla, I.; Myhre, R.; Pitkänen, N.; van Leeuwen, E.M.; Joro, R.; Lagou, V.; Richmond, R.C.; Espinosa, A.; Barton, S.J.; Inskip, H.M.; Holloway, J.W.; Santa-Marina, L.; Estivill, X.; Ang, W.; Marsh, J.A.; Reichetzeder, C.; Marullo, L.; Hocher, B.; Lunetta, K.L.; Murabito, J.M.; Relton, C.L.; Kogevinas, M.; Chatzi, L.; Allard, C.; Bouchard, L.; Hivert, M.F.; Zhang, G.; Muglia, L.J.; Heikkinen, J.; Morgen, C.S.; van Kampen, AHC; van Schaik, BDC; Mentch, F.D.; Langenberg, C.; Luan, J.; Scott, R.A.; Zhao, J.H.; Hemani, G.; Ring, S.M.; Bennett, A.J.; Gaulton, K.J.; Fernandez-Tajes, J.; van Zuydam, N.R.; Medina-Gomez, C.; de Haan, H.G.; Rosendaal, F.R.; Kutalik, Z.; Marques-Vidal, P.; Das, S.; Willemsen, G.; Mbarek, H.; Müller-Nurasyid, M.; Standl, M.; Appel, EVR; Fonvig, C.E.; Trier, C.; van Beijsterveldt, CEM; Murcia, M.; Bustamante, M.; Bonas-Guarch, S.; Hougaard, D.M.; Mercader, J.M.; Linneberg, A.; Schraut, K.E.; Lind, P.A.; Medland, S.E.; Shields, B.M.; Knight, B.A.; Chai, J.F.; Panoutsopoulou, K.; Bartels, M.; Sánchez, F.; Stokholm, J.; Torrents, D.; Vinding, R.K.; Willems, S.M.; Atalay, M.; Chawes, B.L.; Kovacs, P.; Prokopenko, I.; Tuke, M.A.; Yaghootkar, H.; Ruth, K.S.; Jones, S.E.; Loh, P.R.; Murray, A.; Weedon, M.N.; Tönjes, A.; Stumvoll, M.; Michaelsen, K.F.; Eloranta, A.M.; Lakka, T.A.; van Duijn, C.M.; Kiess, W.; Körner, A.; Niinikoski, H.; Pahkala, K.; Raitakari, O.T.; Jacobsson, B.; Zeggini, E.; Dedoussis, G.V.; Teo, Y.Y.; Saw, S.M.; Montgomery, G.W.; Campbell, H.; Wilson, J.F.; Vrijkotte, TGM; Vrijheid, M.; de Geus, EJCN; Hayes, M.G.; Kadarmideen, H.N.; Holm, J.C.; Beilin, L.J.; Pennell, C.E.; Heinrich, J.; Adair, L.S.; Borja, J.B.; Mohlke, K.L.; Eriksson, J.G.; Widén, E.E.; Hattersley, A.T.; Spector, T.D.; Kähönen, M.; Viikari, J.S.; Lehtimäki, T.; Boomsma, D.I.; Sebert, S.; Vollenweider, P.; Sørensen, TIA; Bisgaard, H.; Bønnelykke, K.; Murray, J.C.; Melbye, M.; Nohr, E.A.; Mook-Kanamori, D.O.; Rivadeneira, F.; Hofman, A.; Felix, J.F.; Jaddoe, VWV; Hansen, T.; Pisinger, C.; Vaag, A.A.; Pedersen, O.; Uitterlinden, A.G.; Järvelin, M.R.; Power, C.; Hyppönen, E.; Scholtens, D.M.; Lowe, W.L.; Davey Smith, G.; Timpson, N.J.; Morris, A.P.; Wareham, N.J.; Hakonarson, H.; Grant, SFA; Frayling, T.M.; Lawlor, D.A.; Njølstad, P.R.; Johansson, S.; Ong, K.K.; McCarthy, M.I.; Perry, JRB; Evans, D.M.; Freathy, R.M.

doi:10.1038/s41588-019-0403-1

Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors.

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State: Public
Version: Supplementary document
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Version: Supplementary document
License: CC BY 4.0

Serval ID

serval:BIB_56910884CABD

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors.

Journal

Nature genetics

Author(s)

Warrington N.M., Beaumont R.N., Horikoshi M., Day F.R., Helgeland Ø., Laurin C., Bacelis J., Peng S., Hao K., Feenstra B., Wood A.R., Mahajan A., Tyrrell J., Robertson N.R., Rayner N.W., Qiao Z., Moen G.H., Vaudel M., Marsit C.J., Chen J., Nodzenski M., Schnurr T.M., Zafarmand M.H., Bradfield J.P., Grarup N., Kooijman M.N., Li-Gao R., Geller F., Ahluwalia T.S., Paternoster L., Rueedi R., Huikari V., Hottenga J.J., Lyytikäinen L.P., Cavadino A., Metrustry S., Cousminer D.L., Wu Y., Thiering E., Wang C.A., Have C.T., Vilor-Tejedor N., Joshi P.K., Painter J.N., Ntalla I., Myhre R., Pitkänen N., van Leeuwen E.M., Joro R., Lagou V., Richmond R.C., Espinosa A., Barton S.J., Inskip H.M., Holloway J.W., Santa-Marina L., Estivill X., Ang W., Marsh J.A., Reichetzeder C., Marullo L., Hocher B., Lunetta K.L., Murabito J.M., Relton C.L., Kogevinas M., Chatzi L., Allard C., Bouchard L., Hivert M.F., Zhang G., Muglia L.J., Heikkinen J., Morgen C.S., van Kampen AHC, van Schaik BDC, Mentch F.D., Langenberg C., Luan J., Scott R.A., Zhao J.H., Hemani G., Ring S.M., Bennett A.J., Gaulton K.J., Fernandez-Tajes J., van Zuydam N.R., Medina-Gomez C., de Haan H.G., Rosendaal F.R., Kutalik Z., Marques-Vidal P., Das S., Willemsen G., Mbarek H., Müller-Nurasyid M., Standl M., Appel EVR, Fonvig C.E., Trier C., van Beijsterveldt CEM, Murcia M., Bustamante M., Bonas-Guarch S., Hougaard D.M., Mercader J.M., Linneberg A., Schraut K.E., Lind P.A., Medland S.E., Shields B.M., Knight B.A., Chai J.F., Panoutsopoulou K., Bartels M., Sánchez F., Stokholm J., Torrents D., Vinding R.K., Willems S.M., Atalay M., Chawes B.L., Kovacs P., Prokopenko I., Tuke M.A., Yaghootkar H., Ruth K.S., Jones S.E., Loh P.R., Murray A., Weedon M.N., Tönjes A., Stumvoll M., Michaelsen K.F., Eloranta A.M., Lakka T.A., van Duijn C.M., Kiess W., Körner A., Niinikoski H., Pahkala K., Raitakari O.T., Jacobsson B., Zeggini E., Dedoussis G.V., Teo Y.Y., Saw S.M., Montgomery G.W., Campbell H., Wilson J.F., Vrijkotte TGM, Vrijheid M., de Geus EJCN, Hayes M.G., Kadarmideen H.N., Holm J.C., Beilin L.J., Pennell C.E., Heinrich J., Adair L.S., Borja J.B., Mohlke K.L., Eriksson J.G., Widén E.E., Hattersley A.T., Spector T.D., Kähönen M., Viikari J.S., Lehtimäki T., Boomsma D.I., Sebert S., Vollenweider P., Sørensen TIA, Bisgaard H., Bønnelykke K., Murray J.C., Melbye M., Nohr E.A., Mook-Kanamori D.O., Rivadeneira F., Hofman A., Felix J.F., Jaddoe VWV, Hansen T., Pisinger C., Vaag A.A., Pedersen O., Uitterlinden A.G., Järvelin M.R., Power C., Hyppönen E., Scholtens D.M., Lowe W.L., Davey Smith G., Timpson N.J., Morris A.P., Wareham N.J., Hakonarson H., Grant SFA, Frayling T.M., Lawlor D.A., Njølstad P.R., Johansson S., Ong K.K., McCarthy M.I., Perry JRB, Evans D.M., Freathy R.M.

Working group(s)

EGG Consortium

ISSN

1546-1718 (Electronic)

ISSN-L

1061-4036

Publication state

Published

Issued date

05/2019

Peer-reviewed

Oui

Volume

Number

Pages

804-814

Language

english

Notes

Publication types: Journal Article ; Meta-Analysis
Publication Status: ppublish

Abstract

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.

Keywords

Adult, Birth Weight/genetics, Blood Pressure/genetics, Body Height/genetics, Diabetes Mellitus, Type 2/etiology, Diabetes Mellitus, Type 2/genetics, Female, Fetal Development/genetics, Genetic Predisposition to Disease, Genome-Wide Association Study, Heart Diseases/etiology, Heart Diseases/genetics, Humans, Infant, Newborn, Male, Maternal Inheritance/genetics, Maternal-Fetal Exchange/genetics, Metabolic Diseases/etiology, Metabolic Diseases/genetics, Models, Genetic, Polymorphism, Single Nucleotide, Pregnancy, Risk Factors

URN

urn:nbn:ch:serval-BIB_56910884CABD6

OAI-PMH

oai:serval.unil.ch:BIB_56910884CABD

DOI

10.1038/s41588-019-0403-1

Pubmed

31043758

Web of science

000466842000008

Create date

17/05/2019 9:38