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

Autor: David Torrents, Thorkild I. A. Sørensen, André G. Uitterlinden, Dorret I. Boomsma, Harry Campbell, Vasiliki Lagou, Joachim Heinrich, Anna Murray, Nicholas J. Timpson, George Dedoussis, Beverley M. Shields, Timo A. Lakka, Lawrence J. Beilin, Carmen J. Marsit, Katharina E. Schraut, Marie Standl, Torben Hansen, James F. Wilson, Jonas Bacelis, Allan Vaag, Louis J. Muglia, Wei Ang, Josep M. Mercader, Ruifang Li-Gao, Ying Wu, Jessica Tyrrell, Pål R. Njølstad, Mohammad Hadi Zafarmand, Marie-France Hivert, Ioanna Ntalla, Debbie A Lawlor, Martina Müller-Nurasyid, Alana Cavadino, Natalia Vilor-Tejedor, Andrew R. Wood, Zoltán Kutalik, Jodie N. Painter, Tanja G. M. Vrijkotte, Kyle J. Gaulton, Xavier Estivill, George Davey Smith, Christine Power, Andrew T. Hattersley, Berthold Hocher, Gibran Hemani, Sheila J. Barton, Aino-Maija Eloranta, Kathryn L. Lunetta, Kim F. Michaelsen, Frank Geller, Bjarke Feenstra, Carol A. Wang, Peter Vollenweider, Wieland Kiess, Anubha Mahajan, Elina Hyppönen, Elisabeth M. van Leeuwen, Felix R. Day, Natalie R. van Zuydam, Leda Chatzi, Bo L. Chawes, Antje Körner, Dennis O. Mook-Kanamori, Ken K. Ong, Joanne M. Murabito, David M. Hougaard, Jian'an Luan, Letizia Marullo, Catharina E. M. van Beijsterveldt, Yik Ying Teo, Andrew P. Morris, Sarah E. Medland, Juan Fernández-Tajes, Jouke-Jan Hottenga, Frits R. Rosendaal, Inga Prokopenko, Katja Pahkala, Struan F.A. Grant, Sylvain Sebert, Judith B. Borja, Camilla Schmidt Morgen, Charlotta Pisinger, Jia Chen, Øyvind Helgeland, Christian Theil Have, Vincent W. V. Jaddoe, Marjolein N. Kooijman, Mika Kähönen, Timothy M. Frayling, Diana L. Cousminer, Bo Jacobsson, Antoine H. C. van Kampen, Eco J. C. de Geus, Manolis Kogevinas, Rico Rueedi, Grant W. Montgomery, Raimo Joro, Craig E. Pennell, Jonathan P. Bradfield, Janine F. Felix, Ge Zhang, Loreto Santa-Marina, Kalliope Panoutsopoulou, John R. B. Perry, Jeff Murray, Albert Hofman, Terho Lehtimäki, John W. Holloway, Barbera D. C. van Schaik, Pedro Marques-Vidal, Ronny Myhre, Haja N. Kadarmideen, Robert A. Scott, Frank D. Mentch, Katherine S. Ruth, Hans Bisgaard, Marjo-Riitta Järvelin, Catherine Allard, Rachel M. Freathy, Julie A. Marsh, Mariona Bustamante, Elisabeth Thiering, Cæcilie Trier, Marcus A. Tuke, William L. Lowe, Elisabeth Widen, Caroline L Relton, Christoph Reichetzeder, Penelope A. Lind, M. Geoffrey Hayes, Charles Laurin, Tarunveer S. Ahluwalia, Meike Bartels, Mads Melbye, Claudia Langenberg, Ke Hao, Shouneng Peng, Nicholas J. Wareham, Susan M. Ring, Hamdi Mbarek, Mario Murcia, Jing Hua Zhao, Michael Nodzenski, Cornelia M. van Duijn, Hakon Hakonarson, Hanieh Yaghootkar, Po-Ru Loh, Linda S. Adair, Sílvia Bonàs-Guarch, Eleftheria Zeggini, Sarah Metrustry, Shikta Das, Gonneke Willemsen, Ana Espinosa, Lavinia Paternoster, Marc Vaudel, Theresia M. Schnurr, Michael Stumvoll, David M. Evans, Bridget A. Knight, Luigi Bouchard, Robin N Beaumont, Mustafa Atalay, Zhen Qiao, Denise M. Scholtens, Klaus Bønnelykke, Samuel E. Jones, Peter K. Joshi, Oluf Pedersen, Jin-Fang Chai, Fernando Rivadeneira, Leo-Pekka Lyytikäinen, Rebecca K. Vinding, Hazel Inskip, Sara M. Willems, Cilius Esmann Fonvig, Momoko Horikoshi, Ellen A. Nohr, Jani Heikkinen, Emil V. R. Appel, Niels Grarup, Michael N. Weedon, Rebecca C Richmond, Peter Kovacs, Jorma Viikari, Amanda J. Bennett, Jens-Christian Holm, Carolina Medina-Gomez, Nicole M. Warrington, Anke Tönjes, Jakob Stokholm, Hugoline G. de Haan, Seang-Mei Saw, Ville Huikari, N. William Rayner, Johan G. Eriksson, Niina Pitkänen, Allan Linneberg, Gunn-Helen Moen, Olli T. Raitakari, Martine Vrijheid, Neil Robertson, Stefan Johansson, Tim D. Spector, Friman Sánchez, Mark I. McCarthy, Harri Niinikoski, Karen L. Mohlke
Přispěvatelé: Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, APH - Methodology, Warrington, Nicole M, Beaumont, Robin N, Horikoshi, Momoko, Day, Felix R, Hypponen, E, Freathy, RM, EGG consortium, Medical and Clinical Psychology, University of Helsinki, Johan Eriksson / Principal Investigator, University of Helsinki, Institute for Molecular Medicine Finland, Warrington, Nicole M [0000-0003-4195-775X], Beaumont, Robin N [0000-0003-0750-8248], Day, Felix R [0000-0003-3789-7651], Helgeland, Øyvind [0000-0002-5612-2985], Laurin, Charles [0000-0003-2439-9004], Bacelis, Jonas [0000-0002-2450-732X], Feenstra, Bjarke [0000-0003-1478-649X], Mahajan, Anubha [0000-0001-5585-3420], Moen, Gunn-Helen [0000-0002-8768-0904], Schnurr, Theresia M [0000-0002-6573-4959], Grarup, Niels [0000-0001-5526-1070], Paternoster, Lavinia [0000-0003-2514-0889], Rueedi, Rico [0000-0002-6713-2214], Lyytikäinen, Leo-Pekka [0000-0002-7200-5455], Metrustry, Sarah [0000-0003-2028-7486], Wang, Carol A [0000-0002-4301-3974], Joshi, Peter K [0000-0002-6361-5059], Pitkänen, Niina [0000-0001-7383-4987], Richmond, Rebecca C [0000-0003-0574-5071], Inskip, Hazel M [0000-0001-8897-1749], Holloway, John W [0000-0001-9998-0464], Estivill, Xavier [0000-0002-0723-2256], Hocher, Berthold [0000-0001-8143-0579], Lunetta, Kathryn L [0000-0002-9268-810X], Allard, Catherine [0000-0002-8829-4984], Muglia, Louis J [0000-0002-0301-8770], van Kampen, Antoine HC [0000-0003-1025-7232], van Schaik, Barbera DC [0000-0002-5568-8127], Langenberg, Claudia [0000-0002-5017-7344], Hemani, Gibran [0000-0003-0920-1055], Gaulton, Kyle J [0000-0003-1318-7161], Medina-Gomez, Carolina [0000-0001-7999-5538], Kutalik, Zoltán [0000-0001-8285-7523], Marques-Vidal, Pedro [0000-0002-4548-8500], Mbarek, Hamdi [0000-0002-1108-0371], Müller-Nurasyid, Martina [0000-0003-3793-5910], Appel, Emil VR [0000-0001-7704-6611], Fonvig, Cilius E [0000-0002-5031-0125], Hougaard, David M [0000-0001-5928-3517], Mercader, Josep M [0000-0001-8494-3660], Linneberg, Allan [0000-0002-0994-0184], Lind, Penelope A [0000-0002-3887-2598], Medland, Sarah E [0000-0003-1382-380X], Bartels, Meike [0000-0002-9667-7555], Stokholm, Jakob [0000-0003-4989-9769], Chawes, Bo L [0000-0001-6846-6243], Kovacs, Peter [0000-0002-0290-5423], Prokopenko, Inga [0000-0003-1624-7457], Tuke, Marcus A [0000-0003-0008-9263], Ruth, Katherine S [0000-0003-4966-9170], Jones, Samuel E [0000-0003-0153-922X], Zeggini, Eleftheria [0000-0003-4238-659X], Wilson, James F [0000-0001-5751-9178], Vrijkotte, Tanja GM [0000-0003-3641-4048], de Geus, Eco JCN [0000-0001-6022-2666], Kadarmideen, Haja N [0000-0001-6294-382X], Mohlke, Karen L [0000-0001-6721-153X], Sørensen, Thorkild IA [0000-0003-4821-430X], Bisgaard, Hans [0000-0003-4131-7592], Bønnelykke, Klaus [0000-0003-2003-1018], Melbye, Mads [0000-0001-8264-6785], Rivadeneira, Fernando [0000-0001-9435-9441], Felix, Janine F [0000-0002-9801-5774], Jaddoe, Vincent WV [0000-0003-2939-0041], Hansen, Torben [0000-0001-8748-3831], Hyppönen, Elina [0000-0003-3670-9399], Davey Smith, George [0000-0002-1407-8314], Morris, Andrew P [0000-0002-6805-6014], Hakonarson, Hakon [0000-0003-2814-7461], Grant, Struan FA [0000-0003-2025-5302], Lawlor, Debbie A [0000-0002-6793-2262], Njølstad, Pål R [0000-0003-0304-6728], Ong, Ken K [0000-0003-4689-7530], McCarthy, Mark I [0000-0002-4393-0510], Evans, David M [0000-0003-0663-4621], Freathy, Rachel M [0000-0003-4152-2238], Apollo - University of Cambridge Repository, Department of Medical and Clinical Genetics, Institute for Molecular Medicine Finland, Neuroscience Center, Doctoral Programme Brain & Mind, Ecology and Evolutionary Biology, University of Helsinki, Research Groups, Department of General Practice and Primary Health Care, Research Programs Unit, Diabetes and Obesity Research Program, Johan Eriksson / Principal Investigator, Doctoral Programme in Clinical Research, Doctoral Programme in Oral Sciences, Doctoral Programme in Population Health, Centre of Excellence in Complex Disease Genetics, Elisabeth Ingrid Maria Widen / Principal Investigator, Genomic Discoveries and Clinical Translation, University Management, Epidemiology, Erasmus MC other, Internal Medicine, Pediatrics, Epidemiology and Data Science, APH - Global Health, APH - Aging & Later Life, ACS - Atherosclerosis & ischemic syndromes, ARD - Amsterdam Reproduction and Development, Experimental Immunology, Public and occupational health, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Male
Netherlands Twin Register (NTR)
LD SCORE REGRESSION
Birth Weight/genetics
Physiology
Genome-wide association study
BLOOD-PRESSURE
Blood Pressure
Type 2 diabetes
DISEASE
Fetal Development
0302 clinical medicine
Models
Pregnancy
Risk Factors
Genotype
Birth Weight
maternal genetic
030212 general & internal medicine
Maternal-Fetal Exchange
0303 health sciences
Body Height/genetics
1184 Genetics
developmental biology
physiology
Heart Diseases/etiology
Single Nucleotide
ASSOCIATION
Metabolic Diseases/etiology
3. Good health
Type 2/etiology
MENDELIAN RANDOMIZATION
GROWTH
Female
Maternal Inheritance
Maternal Inheritance/genetics
Adult
Blood Pressure/genetics
Heart Diseases
Offspring
Birth weight
cardio-metabolic health outcomes
Biology
Diabetes Mellitus
Type 2/etiology
Polymorphism
Single Nucleotide
Article
03 medical and health sciences
Genetic
Metabolic Diseases
SDG 3 - Good Health and Well-being
Diabetes mellitus
Mendelian randomization
Genetics
medicine
Diabetes Mellitus
Humans
Genetic Predisposition to Disease
Polymorphism
030304 developmental biology
Glycemic
Fetus
IDENTIFICATION
Models
Genetic
Infant
Newborn
Infant
birth weight
DIABETES-MELLITUS
medicine.disease
Newborn
Fetal Development/genetics
Body Height
Maternal-Fetal Exchange/genetics
LIFE
Blood pressure
Diabetes Mellitus
Type 2
ORIGINS
Institut für Ernährungswissenschaft
030217 neurology & neurosurgery
Genome-Wide Association Study
Zdroj: 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, Marina, L S, 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, A H C, van Schaik, B D C, 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, E V R, Fonvig, C E, Trier, C, van Beijsterveldt, C E M, Murcia, M, Bustamante, M, Bonas-Guarch, S, Hougaard, D M, Mercader, J M, Linneberg, A, Schraut, K, 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, T G M, Vrijheid, M, de Geus, E J C N, 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, Hattersley, A T, Spector, T D, Kähönen, M, Viikari, J S, Lehtimäki, T, Boomsma, D I, Sebert, S, Vollenweider, P, Sørensen, T I A, Bisgaard, H, Bønnelykke, K, Murray, J C, Melbye, M, Nohr, E A, Mook-Kanamori, D O, Rivadeneira, F, Hofman, A, Felix, J F, Jaddoe, V W V, Hansen, T, Pisinger, C, Vaag, A A, Pedersen, O, Uitterlinden, A G, Järvelin, M-R, Power, C, Hyppönen, E, Scholtens, D M, Lowe Jr, W L, Smith, G D, Timpson, N J, Morris, A P, Wareham, N J, Hakonarson, H, Grant, S F A, Frayling, T M, Lawlor, D A, Njølstad, P R, Johansson, S, Ong, K K, McCarthy, M I, Perry, J R B & Evans, D M & Freathy, R M 2019, ' Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors ', Nature Genetics, vol. 51, no. 5, pp. 804–814 . https://doi.org/10.1038/s41588-019-0403-1
Warrington, N M, Li-Gao, R, Hottenga, J J, Willemsen, G, Mbarek, H, van Beijsterveldt, C E M, Bartels, M, de Geus, E J C N, Boomsma, D I, Freathy, R M & EGG Consortium 2019, ' Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors ', Nature Genetics, vol. 51, no. MAY, pp. 804-814 . https://doi.org/10.1038/s41588-019-0403-1
Nature Genetics, 51(MAY), 804-814. Nature Publishing Group
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, Morgen, C S, Fonvig, C E, Nohr, E A, Hansen, T & EGG Consortium 2019, ' Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors ', Nature Genetics, vol. 51, no. 5, pp. 804-814 . https://doi.org/10.1038/s41588-019-0403-1
Nature Genetics, 51(5), 804
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 J 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, Consortium, EGG, Morgen, C S, van Kampen, A H C, van Schaik, B D C, 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, E V R, Fonvig, C E, Trier, C, van Beijsterveldt, C E M, 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, T G M, Vrijheid, M, de Geus, E J C N, 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, T I A, Bisgaard, H F, Bønnelykke, K, Murray, J C, Melbye, M, Nohr, E A, Mook-Kanamori, D O, Rivadeneira, F, Hofman, A, Felix, J F, Jaddoe, V W V, 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, S F A, Frayling, T M, Lawlor, D A, Njølstad, P R, Johansson, S, Ong, K K, McCarthy, M I, Perry, J R B, Evans, D M & Freathy, R M 2019, ' Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors ', Nature Genetics, vol. 51, no. 5, pp. 804-814 . https://doi.org/10.1038/s41588-019-0403-1
Nature Genetics, 51(5), 804-814. Nature Publishing Group
Nature Genetics
EGG Consortium & Morris, A P 2019, ' Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors ', Nature Genetics, vol. 51, no. 5, pp. 804-814 . https://doi.org/10.1038/s41588-019-0403-1
NATURE GENETICS
r-FISABIO. Repositorio Institucional de Producción Científica
instname
Nat. Genet. 51, 804-814 (2019)
r-FISABIO: Repositorio Institucional de Producción Científica
Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
Nature Genetics, 51(5), 804-+. Nature Publishing Group
Nature genetics, 51(5), 804-814. Nature Publishing Group
2019, ' Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors ', Nature Genetics, vol. 51, no. 5, pp. 804-814 . https://doi.org/10.1038/s41588-019-0403-1
ISSN: 1061-4036
DOI: 10.1038/s41588-019-0403-1
Popis: Birth weight (BW) variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. These associations have been proposed to reflect the lifelong consequences of an adverse intrauterine environment. In earlier work, we demonstrated that much of the negative correlation between BW and adult cardio-metabolic traits could instead be attributable to shared genetic effects. However, that work and other previous studies did not systematically distinguish the direct effects of an individual’s own genotype on BW and subsequent disease risk from indirect effects of their mother’s correlated genotype, mediated by the intrauterine environment. Here, we describe expanded genome-wide association analyses of own BW (n=321,223) and offspring BW (n=230,069 mothers), which identified 278 independent association signals influencing BW (214 novel). We used structural equation modelling to decompose the contributions of direct fetal and indirect maternal genetic influences on BW, implicating fetal- and maternal-specific mechanisms. We used Mendelian randomization to explore the causal relationships between factors influencing BW through fetal or maternal routes, for example, glycemic traits and blood pressure. Direct fetal genotype effects dominate the shared genetic contribution to the association between lower BW and higher type 2 diabetes risk, whereas the relationship between lower BW and higher later blood pressure (BP) is driven by a combination of indirect maternal and direct fetal genetic effects: indirect effects of maternal BP-raising genotypes act to reduce offspring BW, but only direct fetal genotype effects (once inherited) increase the offspring’s later BP. Instrumental variable analysis using maternal BW-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring BP. In successfully separating fetal from maternal genetic effects, this work represents an important advance in genetic studies of perinatal outcomes, and shows that the association between lower BW and higher adult BP is attributable to genetic effects, and not to intrauterine programming.
Databáze: OpenAIRE
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