Yan Zheng, Tao Huang, Tiange Wang, Zhendong Mei, Zhonghan Sun, Tao Zhang, Christina Ellervik, Jin-Fang Chai, Xueling Sim, Rob M. van Dam, E-Shyong Tai, Woon-Puay Koh, Rajkumar Dorajoo, Seang-Mei Saw, Charumathi Sabanayagam, Tien Yin Wong, Preeti Gupta, Peter Rossing, Tarunveer S. Ahluwalia, Rebecca K. Vinding, Hans Bisgaard, Klaus Bønnelykke, Yujie Wang, Mariaelisa Graff, Trudy Voortman, Frank J. A. van Rooij, Albert Hofman, Diana van Heemst, Raymond Noordam, Angela C. Estampador, Tibor V. Varga, Cornelia Enzenbach, Markus Scholz, Joachim Thiery, Ralph Burkhardt, Marju Orho-Melander, Christina-Alexandra Schulz, Ulrika Ericson, Emily Sonestedt, Michiaki Kubo, Masato Akiyama, Ang Zhou, Tuomas O. Kilpeläinen, Torben Hansen, Marcus E. Kleber, Graciela Delgado, Mark McCarthy, Rozenn N. Lemaitre, Janine F. Felix, Vincent W. V. Jaddoe, Ying Wu, Karen L. Mohlke, Terho Lehtimäki, Carol A. Wang, Craig E. Pennell, Heribert Schunkert, Thorsten Kessler, Lingyao Zeng, Christina Willenborg, Annette Peters, Wolfgang Lieb, Veit Grote, Peter Rzehak, Berthold Koletzko, Jeanette Erdmann, Matthias Munz, Tangchun Wu, Meian He, Caizheng Yu, Cécile Lecoeur, Philippe Froguel, Dolores Corella, Luis A. Moreno, Chao-Qiang Lai, Niina Pitkänen, Colin A. Boreham, Paul M. Ridker, Frits R. Rosendaal, Renée de Mutsert, Chris Power, Lavinia Paternoster, Thorkild I. A. Sørensen, Anne Tjønneland, Kim Overvad, Luc Djousse, Fernando Rivadeneira, Nanette R. Lee, Olli T. Raitakari, Mika Kähönen, Jorma Viikari, Jean-Paul Langhendries, Joaquin Escribano, Elvira Verduci, George Dedoussis, Inke König, Beverley Balkau, Oscar Coltell, Jean Dallongeville, Aline Meirhaeghe, Philippe Amouyel, Frédéric Gottrand, Katja Pahkala, Harri Niinikoski, Elina Hyppönen, Winfried März, David A. Mackey, Dariusz Gruszfeld, Katherine L. Tucker, Frédéric Fumeron, Ramon Estruch, Jose M. Ordovas, Donna K. Arnett, Dennis O. Mook-Kanamori, Dariush Mozaffarian, Bruce M. Psaty, Kari E. North, Daniel I. Chasman, Lu Qi
Epidemiology studies suggested that low birthweight was associated with a higher risk of hypertension in later life. However, little is known about the causality of such associations. In our study, we evaluated the causal association of low birthweight with adulthood hypertension following a standard analytic protocol using the study-level data of 183,433 participants from 60 studies (CHARGE-BIG consortium), as well as that with blood pressure using publicly available summary-level genome-wide association data from EGG consortium of 153,781 participants, ICBP consortium and UK Biobank cohort together of 757,601 participants. We used seven SNPs as the instrumental variable in the study-level analysis and 47 SNPs in the summary-level analysis. In the study-level analyses, decreased birthweight was associated with a higher risk of hypertension in adults (the odds ratio per 1 standard deviation (SD) lower birthweight, 1.22; 95% CI 1.16 to 1.28), while no association was found between genetically instrumented birthweight and hypertension risk (instrumental odds ratio for causal effect per 1 SD lower birthweight, 0.97; 95% CI 0.68 to 1.41). Such results were consistent with that from the summary-level analyses, where the genetically determined low birthweight was not associated with blood pressure measurements either. One SD lower genetically determined birthweight was not associated with systolic blood pressure (β = − 0.76, 95% CI − 2.45 to 1.08 mmHg), 0.06 mmHg lower diastolic blood pressure (β = − 0.06, 95% CI − 0.93 to 0.87 mmHg), or pulse pressure (β = − 0.65, 95% CI − 1.38 to 0.69 mmHg, all p > 0.05). Our findings suggest that the inverse association of birthweight with hypertension risk from observational studies was not supported by large Mendelian randomization analyses. © 2020, Springer Nature B.V.
Department of Cardiology Zhongshan Hospital, State Key Laboratory of Genetic Engineering School of Life Sciences, Human Phenome Institue, Fudan University, 2005 Songhu Road, Shanghai, 200438, China; Key Laboratory of Public Health Safety of Ministry of Education, School of Public Health, Fudan University, Shanghai, China; Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China; Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, 1440 Canal St, Suite 1724, New Orleans, 70112, LA, United States; Department of Biostatistics, School of Public Health, Shandong University, Jinan, 250012, China; University of Copenhagen, Copenhagen, Denmark; Harvard Medical School, Boston, United States; Department of Production, Research and Innovation, Region Zealand, Denmark; Boston Children’s Hospital, Boston, United States; Saw Swee Hock School of Public Health, National University of Singapore, Singapore, 117549, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Health Services and Systems Research, Duke-NUS Medical School, Singapore, Singapore; Genome Institute of Singapore, Agency for Science Technology and Research, Singapore, Singapore; Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, Singapore; Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore; Steno Diabetes Center Copenhagen (SDCC), Niels Steensens Vej 2, Gentofte, 2820, Denmark; COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark; Department of Epidemiology, University of North Carolina, Chapel Hill, 27514, NC, United States; Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, Netherlands; Department of Epidemiology, Harvard School of Public Health, Boston, MA, United States; Section of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, Netherlands; Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Skåne University Hospital Malmö, Lund University, Malmö, 21741, Sweden; Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany; Institute for Laboratory Medicine, University of Leipzig, Leipzig, Germany; LIFE Research Center for Civilisation Diseases, University of Leipzig, Leipzig, Germany; Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, Regensburg, Germany; Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden; Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama City, Japan; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 2200N, Denmark; Vth Department of Medicine, Mannheim Medical Faculty, Heidelberg University, Mannheim, Germany; Institute of Nutrition, Friedrich Schiller University Jena, Jena, Germany; Competence Cluster of Nutrition and Cardiovascular Health (nutriCARD) Halle-Jena-Leipzig, Copenhagen, Germany; Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, University of Oxford, Old Road, Headington, Oxford, OX3 7LJ, United Kingdom; Department of Medicine, Cardiovascular Health Research Unit, University of Washington, Seattle, 98101, WA, United States; The Generation R Study Group, Erasmus MC, University Medical Center, Rotterdam, Netherlands; Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, Netherlands; Department of Pediatrics, Erasmus MC, University Medical Center, Rotterdam, Netherlands; Department of Genetics, University of North Carolina, Chapel Hill, 27599, NC, United States; Department of Clinical Chemistry, Fimlab Laboratories, Tampere, 33520, Finland; Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere, 33014, Finland; School of Medicine and Public Health, Faculty of Medicine and Health, The University of Newcastle, Callaghan, 2308, NSW, Australia; Deutsches Herzzentrum München, Technische Universität München, Munich, Germany; Institute of Epidemiology and PopGen Biobank, Kiel University, Kiel, Germany; Division of Metabolic and Nutritional Medicine, Dr. Von Hauner Children’s Hospital, Klinikum Der Universitaet Muenchen, Munich, Germany; Institute for Cardiogenetics, University of Lübeck, Lübeck, 23562, Germany; Charité – University Medicine Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute for Dental and Craniofacial Sciences, Department of Periodontology and Synoptic Dentistry, 14197 Berlin, Germany; MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, 430030, Hubei, China; University of Lille Nord de France, CNRS UMR8199, Lille, France; Institut Pasteur de Lille, Lille, France; Department of Preventive Medicine and Public Health, University of Valencia, Valencia, 46022, Spain; CIBER Fisiopatología de La Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, 28029, Spain; Growth Exercise, Nutrition and Development (GENUD) Research Group, Facultad de Ciencias de La Salud, Universidad de Zaragoza, Zaragoza, Spain; USDA ARS, Human Nutrition Research Center on Aging at Tufts University, Boston, 02111, MA, United States; Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, 20520, Finland; UCD Institute for Sport & Health, University College Dublin, Dublin, Ireland; Division of Preventive Medicine, Brigham & Women’s Hospital, Boston, 02215, MA, United States; Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands; Population, Policy and Practice, UCL Institute of Child Health, London, United Kingdom; MRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol, BS82BN, United Kingdom; Department of Public Health, Section of Epidemiology, Faculty of Health and Medical Sciences, University of Copenhagen, 1353K, Copenhagen, Denmark; Danish Cancer Society Research Center, Copenhagen, 2100, Denmark; Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus C, 8000, Denmark; Aalborg University Hospital, Aalborg, 9000, Denmark; Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States; Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands; USC-Office of Population Studies Foundation, Inc., University of San Carlos, Cebu City, 6000, Philippines; Department of Anthropology, Sociology, and History, University of San Carlos, Cebu City, 6000, Philippines; Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, 20521, Finland; Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland; Department of Clinical Physiology, Tampere University Hospital, Tampere, 33521, Finland; Department of Clinical Physiology, Faculty of Medicine and Health Technology, Tampere University, Tampere, 33014, Finland; Division of Medicine, Turku University Hospital, Turku, 20521, Finland; Department of Medicine, University of Turku, Turku, 20520, Finland; Department of Paediatrics and NICU, CHC-Site St-Vincent, Liège-Rocourt, Belgium; Paediatrics Research Unit, Universitat Rovira I Virgili, IISPV, Reus, Spain; Department of Pediatrics, San Paolo Hospital, University of Milan, Milan, Italy; Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece; Institut für Medizinische Biometrie Und Statistik, Universität Zu Lübeck, Lübeck, Germany; INSERM, Centre for Research in Epidemiology and Population Health, U1018, Villejuif, 94807, France; University Versailles Saint-Quentin-en-Yvelines, UMRS 1018, Versailles, 78035, France; University Paris Sud 11, UMRS 1018, Villejuif, 94807, France; Department of Computer Languages and Systems, University Jaume I, Castellon, 12071, Spain; INSERM U1167, Institut Pasteur de Lille, Univ. Lille, Lille, France; INSERM U1286, Hôpital Jeanne de Flandre, CHU Lille, Univ. Lille, Lille, France; Department of Physical Activity and Health, Paavo Nurmi Centre, Sports and Exercise Medicine Unit, Turku, Finland; Department of Pediatrics, Turku University Hospital, Turku, Finland; Department of Physiology, University of Turku, Turku, Finland; Australian Centre for Precision Health, University of South Australia Cancer Research Institute, University of South Australia, Adelaide, Australia; South Australian Health and Medical Research Institute Adelaide, Adelaide, Australia; Synlab Academy, Synlab Holding Deutschland GmbH, Mannheim, Germany; Clinical Institute of Medical and Chemical Laboratory Diagnostics Medical, University of Graz, Graz, Austria; Centre For Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Crawley, Australia; Department of Neonatology and Neonatal Intensive Care, The Children’s Memorial Health Institute, Al. Dzieci Polskich 20, Warsaw, 04-730, Poland; Biomedical and Nutritional Sciences, University of Massachusetts Lowell, Lowell, MA, United States; INSERM, UMR_S 1138, Centre de Recherche Des Cordeliers, Paris, 75006, France; Université de Paris, Centre de Recherche Des Cordeliers UMR-S 1138, Paris, 75006, France; Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1138, Centre de Recherche Des Cordeliers, Paris, 75006, France; Department of Internal Medicine, Hospital Clinic, IDIBAPS, Barcelona, 08036, Spain; IMDEA Food Institute, CEI UAM + CSIC, Madrid, Spain; College of Public Health, University of Kentucky, Lexington, KY, United Kingdom; Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, Netherlands; Friedman School of Nutrition Science & Policy, Tufts University, Boston, 02111, MA, United States; Department of Epidemiology, University of Washington, Seattle, 98101, WA, United States; Department of Health Sciences, University of Washington, Seattle, 98101, WA, United States; Kaiser Permanent Washington Health Research Institute, Seattle, WA, United States; Carolina Center for Genome Sciences, University of North Carolina, Chapel Hill, 27514, NC, United States
