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Association of Birth Weight With Type 2 Diabetes and Glycemic Traits: A Mendelian Randomization Study.
JAMA Netw Open 2019; 2(9):e1910915JN

Abstract

Importance

Observational studies have shown associations of birth weight with type 2 diabetes (T2D) and glycemic traits, but it remains unclear whether these associations represent causal associations.

Objective

To test the association of birth weight with T2D and glycemic traits using a mendelian randomization analysis.

Design, Setting, and Participants

This mendelian randomization study used a genetic risk score for birth weight that was constructed with 7 genome-wide significant single-nucleotide polymorphisms. The associations of this score with birth weight and T2D were tested in a mendelian randomization analysis using study-level data. The association of birth weight with T2D was tested using both study-level data (7 single-nucleotide polymorphisms were used as an instrumental variable) and summary-level data from the consortia (43 single-nucleotide polymorphisms were used as an instrumental variable). Data from 180 056 participants from 49 studies were included.

Main Outcomes and Measures

Type 2 diabetes and glycemic traits.

Results

This mendelian randomization analysis included 49 studies with 41 155 patients with T2D and 80 008 control participants from study-level data and 34 840 patients with T2D and 114 981 control participants from summary-level data. Study-level data showed that a 1-SD decrease in birth weight due to the genetic risk score was associated with higher risk of T2D among all participants (odds ratio [OR], 2.10; 95% CI, 1.69-2.61; P = 4.03 × 10-5), among European participants (OR, 1.96; 95% CI, 1.42-2.71; P = .04), and among East Asian participants (OR, 1.39; 95% CI, 1.18-1.62; P = .04). Similar results were observed from summary-level analyses. In addition, each 1-SD lower birth weight was associated with 0.189 SD higher fasting glucose concentration (β = 0.189; SE = 0.060; P = .002), but not with fasting insulin, 2-hour glucose, or hemoglobin A1c concentration.

Conclusions and Relevance

In this study, a genetic predisposition to lower birth weight was associated with increased risk of T2D and higher fasting glucose concentration, suggesting genetic effects on retarded fetal growth and increased diabetes risk that either are independent of each other or operate through alterations of integrated biological mechanisms.

Authors+Show Affiliations

No affiliation info availableKey Laboratory of Molecular Cardiovascular Sciences, Peking University, Ministry of Education, Beijing, China. Department of Global Health, School of Public Health, Peking University, Beijing, China. Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China.Shanghai Institute of Endocrine and Metabolic Diseases, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana.Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. School of Life Sciences, Fudan University, Shanghai, China.Department of Research and Innovation Region Zealand, Region Zealand, Denmark. Division of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Department of Laboratory Medicine, Boston Children's Hospital, Boston, Massachusetts. Department of Pathology, Harvard Medical School, Boston, Massachusetts.Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana.Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China.Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China.Saw Swee Hock School of Public Health, National University of Singapore, Singapore.Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark. Steno Diabetes Center Copenhagen, Gentofte, Denmark.Department of Epidemiology, University of North Carolina, Chapel Hill.Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, Netherlands.Section of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, Netherlands.Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas.LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany. Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.RIKEN Center for Integrative Medical Sciences, Laboratory for Statistical Analysis, Yokohama, Japan.Genome Institute of Singapore, Agency for Science Technology and Research, Singapore.Centre for Population Health Research, School of Health Sciences, University of South Australia, Adelaide, Australia. Sansom Institute of Health Research, University of South Australia, Adelaide, Australia.The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.Competence Cluster of Nutrition and Cardiovascular Health, Halle-Jena-Leipzig, Germany. Institute of Nutrition, Friedrich Schiller University, Jena, Germany. Vth Department of Medicine, Mannheim Medical Faculty, Heidelberg University, Mannheim, Germany.MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, United Kingdom.MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, United Kingdom. NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, University of Southampton, Southampton, United Kingdom.Cardiovascular Health Research Institute, Department of Medicine, University of Washington, Seattle.The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands. Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands. Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands.Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.Genome Institute of Singapore, Agency for Science Technology and Research, Singapore.Department of Clinical Chemistry, Fimlab Laboratories, and Finnish Cardiovascular Research Center, Tampere, Finland. Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.Division of Obstetrics and Gynaecology, School of Medicine, University of Western Australia, Crawley, Western Australia, Australia. Department of Obstetrics and Gynecology, School of Medicine and Public Health, The University of Newcastle, Callaghan, New South Wales, Australia.Ludwig-Maximilians-University of Munich, Dr von Hauner Children's Hospital, Division of Metabolic Diseases and Nutritional Medicine, Munich, Germany. Institute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.Institute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany. Division of Metabolic and Nutritional Medicine, Dr von Hauner Children's Hospital, Klinikum der Universitaet Muenchen, Munich, Germany.Institute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.Division of Metabolic and Nutritional Medicine, Dr von Hauner Children's Hospital, Klinikum der Universitaet Muenchen, Munich, Germany.William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, China.University of Lille Nord de France, Lille, France. Institut Pasteur de Lille, Lille, France.Department of Preventive Medicine and Public Health, University of Valencia, Valencia, Spain. CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain.United States Department of Agriculture Research Service, Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts.CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain. Growth Exercise, Nutrition and Development Research Group, Facultad de Ciencias de la Salud, Universidad de Zaragoza, Zaragoza, Spain.Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.UCD Institute for Sport & Health, University College Dublin, Dublin, Ireland.Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana. Department of Biostatistics, School of Public Health, Shandong University, Jinan, China.Saw Swee Hock School of Public Health, National University of Singapore, Singapore. Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.Division of Preventive Medicine, Brigham & Women's Hospital, Boston, Massachusetts.Department of Epidemiology, University of North Carolina, Chapel Hill.Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, Netherlands.Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, Netherlands.Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, Netherlands. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.Section of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, Netherlands.Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands.Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands.LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany. Institute for Laboratory Medicine, University of Leipzig, Leipzig, Germany.Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.RIKEN Center for Integrative Medical Sciences, Laboratory for Statistical Analysis, Yokohama, Japan.Division of Cancer Control and Population Sciences, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania. Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.Population, Policy and Practice, UCL Great Ormond Street Institute of Child Health, London, United Kingdom.The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Department of Public Health, Section of Epidemiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. MRC Integrative Epidemiology Unit & School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.Danish Cancer Society Research Center, Copenhagen, Denmark.Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark. Aalborg University Hospital, Aalborg, Denmark.Vth Department of Medicine, Mannheim Medical Faculty, Heidelberg University, Mannheim, Germany.MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, United Kingdom. NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, University of Southampton, Southampton, United Kingdom. Oxford NIHR Musculoskeletal Biomedical Research Unit, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, The Botnar Research Centre, University of Oxford, Oxford, United Kingdom.Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands. Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands. Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands.MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, United Kingdom.Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.Saw Swee Hock School of Public Health, National University of Singapore, Singapore. Genome Institute of Singapore, Agency for Science Technology and Research, Singapore.USC Office of Population Studies Foundation Inc, University of San Carlos, Cebu City, Philippines. Department of Anthropology, Sociology, and History, University of San Carlos, Cebu City, Philippines.Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland. Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.Department of Clinical Physiology, Tampere University Hospital, and Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.Division of Medicine, Turku University Hospital, Turku, Finland. Department of Medicine, University of Turku, Turku, Finland.Division of Metabolic and Nutritional Medicine, Dr von Hauner Children's Hospital, Klinikum der Universitaet Muenchen, Munich, Germany.Department of Paediatrics and NICU, CHC-Site St-Vincent, Liège-Rocourt, Belgium.Division of Metabolic and Nutritional Medicine, Dr von Hauner Children's Hospital, Klinikum der Universitaet Muenchen, Munich, Germany.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.MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, China.Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.Singapore Eye Research Institute, Singapore National Eye Centre, Singapore. Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.University of Lille Nord de France, Lille, France. Institut Pasteur de Lille, Lille, France. University of Lille Nord de France, Lille, France.INSERM, Centre for Research in Epidemiology and Population Health, Villejuif, France. University Versailles Saint-Quentin-en-Yvelines, Versailles, France. University Paris Sud 11, Villejuif, France.Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain. Department of Computer Languages and Systems, University Jaume I, Castellon, Spain.INSERM U1167, Institut Pasteur de Lille, University of Lille, Lille, France.INSERM U995, Hôpital Jeanne de Flandre, CHU-Lille, University of Lille, Lille, France.Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland. Paavo Nurmi Centre, Sports and Exercise Medicine Unit, Department of Physical Activity and Health, Turku, Finland.Department of Pediatrics, Turku University Hospital, Turku, Finland. Department of Physiology, University of Turku, Turku, Finland.Population, Policy and Practice, UCL Great Ormond Street Institute of Child Health, London, United Kingdom. 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, Australia.The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.Vth Department of Medicine, Mannheim Medical Faculty, Heidelberg University, Mannheim, Germany. Synlab Academy, Synlab Holding Deutschland GmbH, Mannheim, Germany. Clinical Institute of Medical and Chemical Laboratory Diagnostics Medical University of Graz, Graz, Austria.MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, United Kingdom. NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, University of Southampton, Southampton, United Kingdom.The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands. Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands. Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands.MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, United Kingdom. Victoria University of Wellington, Wellington, New Zealand.Singapore Eye Research Institute, Singapore National Eye Centre, Singapore. Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore.Singapore Eye Research Institute, Singapore National Eye Centre, Singapore. Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore.Saw Swee Hock School of Public Health, National University of Singapore, Singapore. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Health Services and Systems Research, Duke-NUS Medical School, Singapore.Department of Genetics, University of North Carolina, Chapel Hill.Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Crawley, Western Australia, Australia.Department of Neonatology and Neonatal Intensive Care, The Children's Memorial Health Institute, Al. Dzieci Polskich 20, Warsaw, Poland.William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom. Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD) King Abdulaziz University, Jeddah, Saudi Arabia.Biomedical and Nutritional Sciences, University of Massachusetts, Lowell.INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, Paris, France. University of Paris Diderot, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers, Paris, France. Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1138, Centre de Recherche des Cordeliers, Paris, France.Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.Steno Diabetes Center Copenhagen, Gentofte, Denmark.CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain. Department of Internal Medicine, Hospital Clinic, IDIBAPS, Barcelona, Spain.United States Department of Agriculture Research Service, Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts. Department of Epidemiology and Population Genetics, Centro Nacional Investigación, Cardiovasculares (CNIC), Madrid, Spain.College of Public Health, University of Kentucky, Lexington.INSERM U1167, Institut Pasteur de Lille, University of Lille, Lille, France.INSERM U1167, Institut Pasteur de Lille, University of Lille, Lille, France.Singapore Eye Research Institute, Singapore National Eye Centre, Singapore. Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore.Saw Swee Hock School of Public Health, National University of Singapore, Singapore.Saw Swee Hock School of Public Health, National University of Singapore, Singapore. Department of Statistics and Applied Probability, Faculty of Science, National University of Singapore, Singapore.Saw Swee Hock School of Public Health, National University of Singapore, Singapore.Saw Swee Hock School of Public Health, National University of Singapore, Singapore. Health Services and Systems Research, Duke-NUS Medical School, Singapore.Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany. Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.RIKEN Center for Integrative Medical Sciences, Laboratory for Statistical Analysis, Yokohama, Japan.LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany. Institute for Laboratory Medicine, University of Leipzig, Leipzig, Germany.Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands. Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, Netherlands.Friedman School of Nutrition Science & Policy, Tufts University, Boston, Massachusetts.Cardiovascular Health Research Institute, Department of Medicine, University of Washington, Seattle. Department of Epidemiology, University of Washington, Seattle. Department of Health Sciences, University of Washington, Seattle. Kaiser Permanent Washington Health Research Institute, Seattle.Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, Netherlands.MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, China.Department of Epidemiology, University of North Carolina, Chapel Hill. Carolina Center for Genome Sciences, University of North Carolina, Chapel Hill.MRC Integrative Epidemiology Unit & School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.Division of Preventive Medicine, Brigham & Women's Hospital, Boston, Massachusetts. Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31539074

Citation

BIRTH-GENE (BIG) Study Working Group, et al. "Association of Birth Weight With Type 2 Diabetes and Glycemic Traits: a Mendelian Randomization Study." JAMA Network Open, vol. 2, no. 9, 2019, pp. e1910915.
BIRTH-GENE (BIG) Study Working Group, Huang T, Wang T, et al. Association of Birth Weight With Type 2 Diabetes and Glycemic Traits: A Mendelian Randomization Study. JAMA Netw Open. 2019;2(9):e1910915.
Huang, T., Wang, T., Zheng, Y., Ellervik, C., Li, X., Gao, M., ... Qi, L. (2019). Association of Birth Weight With Type 2 Diabetes and Glycemic Traits: A Mendelian Randomization Study. JAMA Network Open, 2(9), pp. e1910915. doi:10.1001/jamanetworkopen.2019.10915.
BIRTH-GENE (BIG) Study Working Group, et al. Association of Birth Weight With Type 2 Diabetes and Glycemic Traits: a Mendelian Randomization Study. JAMA Netw Open. 2019 Sep 4;2(9):e1910915. PubMed PMID: 31539074.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of Birth Weight With Type 2 Diabetes and Glycemic Traits: A Mendelian Randomization Study. AU - ,, AU - Huang,Tao, AU - Wang,Tiange, AU - Zheng,Yan, AU - Ellervik,Christina, AU - Li,Xiang, AU - Gao,Meng, AU - Fang,Zhe, AU - Chai,Jin-Fang, AU - Ahluwalia,Tarun Veer S, AU - Wang,Yujie, AU - Voortman,Trudy, AU - Noordam,Raymond, AU - Frazier-Wood,Alexis, AU - Scholz,Markus, AU - Sonestedt,Emily, AU - Akiyama,Masato, AU - Dorajoo,Rajkumar, AU - Zhou,Ang, AU - Kilpeläinen,Tuomas O, AU - Kleber,Marcus E, AU - Crozier,Sarah R, AU - Godfrey,Keith M, AU - Lemaitre,Rozenn, AU - Felix,Janine F, AU - Shi,Yuan, AU - Gupta,Preeti, AU - Khor,Chiea-Chuen, AU - Lehtimäki,Terho, AU - Wang,Carol A, AU - Tiesler,Carla M T, AU - Thiering,Elisabeth, AU - Standl,Marie, AU - Rzehak,Peter, AU - Marouli,Eirini, AU - He,Meian, AU - Lecoeur,Cécile, AU - Corella,Dolores, AU - Lai,Chao-Qiang, AU - Moreno,Luis A, AU - Pitkänen,Niina, AU - Boreham,Colin A, AU - Zhang,Tao, AU - Saw,Seang Mei, AU - Ridker,Paul M, AU - Graff,Mariaelisa, AU - van Rooij,Frank J A, AU - Uitterlinden,Andre G, AU - Hofman,Albert, AU - van Heemst,Diana, AU - Rosendaal,Frits R, AU - de Mutsert,Renée, AU - Burkhardt,Ralph, AU - Schulz,Christina-Alexandra, AU - Ericson,Ulrika, AU - Kamatani,Yoichiro, AU - Yuan,Jian-Min, AU - Power,Chris, AU - Hansen,Torben, AU - Sørensen,Thorkild I A, AU - Tjønneland,Anne, AU - Overvad,Kim, AU - Delgado,Graciela, AU - Cooper,Cyrus, AU - Djousse,Luc, AU - Rivadeneira,Fernando, AU - Jameson,Karen, AU - Zhao,Wanting, AU - Liu,Jianjun, AU - Lee,Nanette R, AU - Raitakari,Olli, AU - Kähönen,Mika, AU - Viikari,Jorma, AU - Grote,Veit, AU - Langhendries,Jean-Paul, AU - Koletzko,Berthold, AU - Escribano,Joaquin, AU - Verduci,Elvira, AU - Dedoussis,George, AU - Yu,Caizheng, AU - Tham,Yih Chung, AU - Lim,Blanche, AU - Lim,Sing Hui, AU - Froguel,Philippe, AU - Balkau,Beverley, AU - Fink,Nadia R, AU - Vinding,Rebecca K, AU - Sevelsted,Astrid, AU - Bisgaard,Hans, AU - Coltell,Oscar, AU - Dallongeville,Jean, AU - Gottrand,Frédéric, AU - Pahkala,Katja, AU - Niinikoski,Harri, AU - Hyppönen,Elina, AU - Pedersen,Oluf, AU - März,Winfried, AU - Inskip,Hazel, AU - Jaddoe,Vincent W V, AU - Dennison,Elaine, AU - Wong,Tien Yin, AU - Sabanayagam,Charumathi, AU - Tai,E-Shyong, AU - Mohlke,Karen L, AU - Mackey,David A, AU - Gruszfeld,Dariusz, AU - Deloukas,Panagiotis, AU - Tucker,Katherine L, AU - Fumeron,Frédéric, AU - Bønnelykke,Klaus, AU - Rossing,Peter, AU - Estruch,Ramon, AU - Ordovas,Jose M, AU - Arnett,Donna K, AU - Meirhaeghe,Aline, AU - Amouyel,Philippe, AU - Cheng,Ching-Yu, AU - Sim,Xueling, AU - Teo,Yik Ying, AU - van Dam,Rob M, AU - Koh,Woon-Puay, AU - Orho-Melander,Marju, AU - Loeffler,Markus, AU - Kubo,Michiaki, AU - Thiery,Joachim, AU - Mook-Kanamori,Dennis O, AU - Mozaffarian,Dariush, AU - Psaty,Bruce M, AU - Franco,Oscar H, AU - Wu,Tangchun, AU - North,Kari E, AU - Davey Smith,George, AU - Chavarro,Jorge E, AU - Chasman,Daniel I, AU - Qi,Lu, Y1 - 2019/09/04/ PY - 2019/9/21/entrez PY - 2019/9/21/pubmed PY - 2019/9/21/medline SP - e1910915 EP - e1910915 JF - JAMA network open JO - JAMA Netw Open VL - 2 IS - 9 N2 - Importance: Observational studies have shown associations of birth weight with type 2 diabetes (T2D) and glycemic traits, but it remains unclear whether these associations represent causal associations. Objective: To test the association of birth weight with T2D and glycemic traits using a mendelian randomization analysis. Design, Setting, and Participants: This mendelian randomization study used a genetic risk score for birth weight that was constructed with 7 genome-wide significant single-nucleotide polymorphisms. The associations of this score with birth weight and T2D were tested in a mendelian randomization analysis using study-level data. The association of birth weight with T2D was tested using both study-level data (7 single-nucleotide polymorphisms were used as an instrumental variable) and summary-level data from the consortia (43 single-nucleotide polymorphisms were used as an instrumental variable). Data from 180 056 participants from 49 studies were included. Main Outcomes and Measures: Type 2 diabetes and glycemic traits. Results: This mendelian randomization analysis included 49 studies with 41 155 patients with T2D and 80 008 control participants from study-level data and 34 840 patients with T2D and 114 981 control participants from summary-level data. Study-level data showed that a 1-SD decrease in birth weight due to the genetic risk score was associated with higher risk of T2D among all participants (odds ratio [OR], 2.10; 95% CI, 1.69-2.61; P = 4.03 × 10-5), among European participants (OR, 1.96; 95% CI, 1.42-2.71; P = .04), and among East Asian participants (OR, 1.39; 95% CI, 1.18-1.62; P = .04). Similar results were observed from summary-level analyses. In addition, each 1-SD lower birth weight was associated with 0.189 SD higher fasting glucose concentration (β = 0.189; SE = 0.060; P = .002), but not with fasting insulin, 2-hour glucose, or hemoglobin A1c concentration. Conclusions and Relevance: In this study, a genetic predisposition to lower birth weight was associated with increased risk of T2D and higher fasting glucose concentration, suggesting genetic effects on retarded fetal growth and increased diabetes risk that either are independent of each other or operate through alterations of integrated biological mechanisms. SN - 2574-3805 UR - https://www.unboundmedicine.com/medline/citation/31539074/Association_of_Birth_Weight_With_Type_2_Diabetes_and_Glycemic_Traits:_A_Mendelian_Randomization_Study L2 - https://jamanetwork.com/journals/jamanetworkopen/fullarticle/10.1001/jamanetworkopen.2019.10915 DB - PRIME DP - Unbound Medicine ER -