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

TitreMaternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors.
Publication TypeJournal Article
Year of Publication2019
AuthorsWarrington, NM, Beaumont, RN, Horikoshi, M, Day, FR, Helgeland, Ø, Laurin, C, Bacelis, J, Peng, S, Hao, K, Feenstra, B, Wood, AR, Mahajan, A, Tyrrell, J, Robertson, NR, N Rayner, W, Qiao, Z, Moen, G-H, Vaudel, M, Marsit, CJ, Chen, J, Nodzenski, M, Schnurr, TM, Zafarmand, MH, Bradfield, JP, Grarup, N, Kooijman, MN, Li-Gao, R, Geller, F, Ahluwalia, TS, Paternoster, L, Rueedi, R, Huikari, V, Hottenga, J-J, Lyytikainen, L-P, Cavadino, A, Metrustry, S, Cousminer, DL, Wu, Y, Thiering, E, Wang, CA, Have, CT, Vilor-Tejedor, N, Joshi, PK, Painter, JN, Ntalla, I, Myhre, R, Pitkänen, N, van Leeuwen, EM, Joro, R, Lagou, V, Richmond, RC, Espinosa, A, Barton, SJ, Inskip, HM, Holloway, JW, Santa-Marina, L, Estivill, X, Ang, W, Marsh, JA, Reichetzeder, C, Marullo, L, Hocher, B, Lunetta, KL, Murabito, JM, Relton, CL, Kogevinas, M, Chatzi, L, Allard, C, Bouchard, L, Hivert, M-F, Zhang, G, Muglia, LJ, Heikkinen, J, Morgen, CS, van Kampen, AHC, van Schaik, BDC, Mentch, FD, Langenberg, C, Luan, J'an, Scott, RA, Zhao, JHua, Hemani, G, Ring, SM, Bennett, AJ, Gaulton, KJ, Fernandez-Tajes, J, van Zuydam, NR, Medina-Gomez, C, de Haan, HG, Rosendaal, FR, Kutalik, Z, Marques-Vidal, P, Das, S, Willemsen, G, Mbarek, H, Müller-Nurasyid, M, Standl, M, Appel, EVR, Fonvig, CE, Trier, C, van Beijsterveldt, CEM, Murcia, M, Bustamante, M, Bonas-Guarch, S, Hougaard, DM, Mercader, JM, Linneberg, A, Schraut, KE, Lind, PA, Medland, SE, Shields, BM, Knight, BA, Chai, J-F, Panoutsopoulou, K, Bartels, M, Sánchez, F, Stokholm, J, Torrents, D, Vinding, RK, Willems, SM, Atalay, M, Chawes, BL, Kovacs, P, Prokopenko, I, Tuke, MA, Yaghootkar, H, Ruth, KS, Jones, SE, Loh, P-R, Murray, A, Weedon, MN, Tonjes, A, Stumvoll, M, Michaelsen, KF, Eloranta, A-M, Lakka, TA, van Duijn, CM, Kiess, W, Körner, A, Niinikoski, H, Pahkala, K, Raitakari, OT, Jacobsson, B, Zeggini, E, Dedoussis, GV, Teo, Y-Y, Saw, S-M, Montgomery, GW, Campbell, H, Wilson, JF, Vrijkotte, TGM, Vrijheid, M, de Geus, EJCN, M Hayes, G, Kadarmideen, HN, Holm, J-C, Beilin, LJ, Pennell, CE, Heinrich, J, Adair, LS, Borja, JB, Mohlke, KL, Eriksson, JG, Widén, EE, Hattersley, AT, Spector, TD, Kahonen, M, Viikari, JS, Lehtimaki, T, Boomsma, DI, Sebert, S, Vollenweider, P, Sørensen, TIA, Bisgaard, H, Bønnelykke, K, Murray, JC, Melbye, M, Nohr, EA, Mook-Kanamori, DO, Rivadeneira, F, Hofman, A, Felix, JF, Jaddoe, VWV, Hansen, T, Pisinger, C, Vaag, AA, Pedersen, O, Uitterlinden, AG, Jarvelin, M-R, Power, C, Hypponen, E, Scholtens, DM, Lowe, WL, Smith, GDavey, Timpson, NJ, Morris, AP, Wareham, NJ, Hakonarson, H, Grant, SFA, Frayling, TM, Lawlor, DA, Njølstad, PR, Johansson, S, Ong, KK, McCarthy, MI, Perry, JRB, Evans, DM, Freathy, RM
Corporate AuthorsEGG Consortium
JournalNature genetics
Volume51
Issue5
Pagination804-814
Date Published05/2019
DOI10.1038/s41588-019-0403-1
ISSN1546-1718
Mots-clésAdult, Birth Weight/genetics, Blood Pressure/genetics, Body Height/genetics, Diabetes Mellitus, Female, Fetal Development/genetics, Genetic, Genetic Predisposition to Disease, Genome-Wide Association Study, Heart Diseases/etiology, Heart Diseases/genetics, Humans, Infant, Male, Maternal Inheritance/genetics, Maternal-Fetal Exchange/genetics, Metabolic Diseases/etiology, Metabolic Diseases/genetics, Models, Newborn, polymorphism, Pregnancy, Risk Factors, Single Nucleotide, Type 2/etiology, Type 2/genetics
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.

Alternate URL

https://www.ncbi.nlm.nih.gov/pubmed/31043758?dopt=Abstract

WOS ID (UT)

000466842000008

Alternate JournalNat. Genet.
Citation Key / SERVAL ID9556
Peer reviewRefereed
PubMed ID31043758
PubMed Central IDPMC6522365
Grant ListR24 ES028507 / ES / NIEHS NIH HHS / United States
202802 / / Wellcome Trust / United Kingdom
MR/M005070/1 / / Medical Research Council / United Kingdom
088806 / / Wellcome Trust / United Kingdom
104150 / / Wellcome Trust / United Kingdom
R01 ES022223 / ES / NIEHS NIH HHS / United States
212259 / / Wellcome Trust / United Kingdom
098395 / / Wellcome Trust / United Kingdom
205915 / / Wellcome Trust / United Kingdom
R01 ES029212 / ES / NIEHS NIH HHS / United States
17/0005594 / / Diabetes UK / United Kingdom
323195 / / European Research Council / International
P30 ES019776 / ES / NIEHS NIH HHS / United States
MC_UU_12011/4 / / Medical Research Council / United Kingdom
098381 / / Wellcome Trust / United Kingdom

                         

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