Format

Send to

Choose Destination
JAMA Netw Open. 2019 Sep 4;2(9):e1910915. doi: 10.1001/jamanetworkopen.2019.10915.

Association of Birth Weight With Type 2 Diabetes and Glycemic Traits: A Mendelian Randomization Study.

BIRTH-GENE (BIG) Study Working Group, Huang T1,2,3, Wang T4,5,6, Zheng Y5,7, Ellervik C8,9,10,11, Li X6, Gao M3, Fang Z3, Chai JF12, Ahluwalia TVS13,14, Wang Y15, Voortman T16, Noordam R17, Frazier-Wood A18, Scholz M19,20, Sonestedt E21, Akiyama M22, Dorajoo R23, Zhou A24,25, Kilpeläinen TO26, Kleber ME27,28,29, Crozier SR30, Godfrey KM30,31, Lemaitre R32, Felix JF33,34,35, Shi Y36, Gupta P36, Khor CC23, Lehtimäki T37,38, Wang CA39,40, Tiesler CMT41,42, Thiering E42,43, Standl M42, Rzehak P43, Marouli E44, He M45, Lecoeur C46,47, Corella D48,49, Lai CQ50, Moreno LA49,51, Pitkänen N52, Boreham CA53, Zhang T6,54, Saw SM12,36, Ridker PM55, Graff M15, van Rooij FJA16, Uitterlinden AG56, Hofman A16,57, van Heemst D17, Rosendaal FR58, de Mutsert R58, Burkhardt R19,59, Schulz CA21, Ericson U21, Kamatani Y22, Yuan JM60,61, Power C62, Hansen T26, Sørensen TIA26,63,64, Tjønneland A65, Overvad K66,67, Delgado G29, Cooper C30,31,68, Djousse L69, Rivadeneira F33,34,70, Jameson K30, Zhao W36, Liu J12,23, Lee NR71,72, Raitakari O52,73, Kähönen M74, Viikari J75,76, Grote V43, Langhendries JP77, Koletzko B43, Escribano J78, Verduci E79, Dedoussis G80, Yu C45, Tham YC36, Lim B36,81, Lim SH36, Froguel P46,47,46, Balkau B82,83,84, Fink NR13, Vinding RK13, Sevelsted A13, Bisgaard H13, Coltell O49,85, Dallongeville J86, Gottrand F87, Pahkala K52,88, Niinikoski H89,90, Hyppönen E62,91,92, Pedersen O26, März W29,93,94, Inskip H30,31, Jaddoe VWV33,34,35, Dennison E30,95, Wong TY36,81,96, Sabanayagam C36,96, Tai ES12,97,98, Mohlke KL99, Mackey DA100, Gruszfeld D101, Deloukas P44,102, Tucker KL103, Fumeron F104,105,106, Bønnelykke K13, Rossing P14, Estruch R49,107, Ordovas JM50,108, Arnett DK109, Meirhaeghe A86, Amouyel P86, Cheng CY36,81,96, Sim X12, Teo YY12,110, van Dam RM12, Koh WP12,98, Orho-Melander M21, Loeffler M19,20, Kubo M22, Thiery J19,59, Mook-Kanamori DO58,111, Mozaffarian D112, Psaty BM32,113,114,115, Franco OH16, Wu T45, North KE15,116, Davey Smith G64, Chavarro JE5,57, Chasman DI55,69, Qi L5,6.

Author information

1
Key Laboratory of Molecular Cardiovascular Sciences, Peking University, Ministry of Education, Beijing, China.
2
Department of Global Health, School of Public Health, Peking University, Beijing, China.
3
Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China.
4
Shanghai Institute of Endocrine and Metabolic Diseases, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
5
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
6
Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana.
7
School of Life Sciences, Fudan University, Shanghai, China.
8
Department of Research and Innovation Region Zealand, Region Zealand, Denmark.
9
Division of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
10
Department of Laboratory Medicine, Boston Children's Hospital, Boston, Massachusetts.
11
Department of Pathology, Harvard Medical School, Boston, Massachusetts.
12
Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
13
Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
14
Steno Diabetes Center Copenhagen, Gentofte, Denmark.
15
Department of Epidemiology, University of North Carolina, Chapel Hill.
16
Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, Netherlands.
17
Section of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, Netherlands.
18
Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas.
19
LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany.
20
Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
21
Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
22
RIKEN Center for Integrative Medical Sciences, Laboratory for Statistical Analysis, Yokohama, Japan.
23
Genome Institute of Singapore, Agency for Science Technology and Research, Singapore.
24
Centre for Population Health Research, School of Health Sciences, University of South Australia, Adelaide, Australia.
25
Sansom Institute of Health Research, University of South Australia, Adelaide, Australia.
26
The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
27
Competence Cluster of Nutrition and Cardiovascular Health, Halle-Jena-Leipzig, Germany.
28
Institute of Nutrition, Friedrich Schiller University, Jena, Germany.
29
Vth Department of Medicine, Mannheim Medical Faculty, Heidelberg University, Mannheim, Germany.
30
MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, United Kingdom.
31
NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, University of Southampton, Southampton, United Kingdom.
32
Cardiovascular Health Research Institute, Department of Medicine, University of Washington, Seattle.
33
The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands.
34
Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands.
35
Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands.
36
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
37
Department of Clinical Chemistry, Fimlab Laboratories, and Finnish Cardiovascular Research Center, Tampere, Finland.
38
Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
39
Division of Obstetrics and Gynaecology, School of Medicine, University of Western Australia, Crawley, Western Australia, Australia.
40
Department of Obstetrics and Gynecology, School of Medicine and Public Health, The University of Newcastle, Callaghan, New South Wales, Australia.
41
Ludwig-Maximilians-University of Munich, Dr von Hauner Children's Hospital, Division of Metabolic Diseases and Nutritional Medicine, Munich, Germany.
42
Institute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
43
Division of Metabolic and Nutritional Medicine, Dr von Hauner Children's Hospital, Klinikum der Universitaet Muenchen, Munich, Germany.
44
William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
45
MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, China.
46
University of Lille Nord de France, Lille, France.
47
Institut Pasteur de Lille, Lille, France.
48
Department of Preventive Medicine and Public Health, University of Valencia, Valencia, Spain.
49
CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain.
50
United States Department of Agriculture Research Service, Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts.
51
Growth Exercise, Nutrition and Development Research Group, Facultad de Ciencias de la Salud, Universidad de Zaragoza, Zaragoza, Spain.
52
Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
53
UCD Institute for Sport & Health, University College Dublin, Dublin, Ireland.
54
Department of Biostatistics, School of Public Health, Shandong University, Jinan, China.
55
Division of Preventive Medicine, Brigham & Women's Hospital, Boston, Massachusetts.
56
Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, Netherlands.
57
Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
58
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands.
59
Institute for Laboratory Medicine, University of Leipzig, Leipzig, Germany.
60
Division of Cancer Control and Population Sciences, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
61
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.
62
Population, Policy and Practice, UCL Great Ormond Street Institute of Child Health, London, United Kingdom.
63
Department of Public Health, Section of Epidemiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
64
MRC Integrative Epidemiology Unit & School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
65
Danish Cancer Society Research Center, Copenhagen, Denmark.
66
Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark.
67
Aalborg University Hospital, Aalborg, Denmark.
68
Oxford NIHR Musculoskeletal Biomedical Research Unit, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, The Botnar Research Centre, University of Oxford, Oxford, United Kingdom.
69
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
70
Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands.
71
USC Office of Population Studies Foundation Inc, University of San Carlos, Cebu City, Philippines.
72
Department of Anthropology, Sociology, and History, University of San Carlos, Cebu City, Philippines.
73
Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
74
Department of Clinical Physiology, Tampere University Hospital, and Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
75
Division of Medicine, Turku University Hospital, Turku, Finland.
76
Department of Medicine, University of Turku, Turku, Finland.
77
Department of Paediatrics and NICU, CHC-Site St-Vincent, Liège-Rocourt, Belgium.
78
Paediatrics Research Unit, Universitat Rovira i Virgili, IISPV, Reus, Spain.
79
Department of Pediatrics, San Paolo Hospital, University of Milan, Milan, Italy.
80
Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece.
81
Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
82
INSERM, Centre for Research in Epidemiology and Population Health, Villejuif, France.
83
University Versailles Saint-Quentin-en-Yvelines, Versailles, France.
84
University Paris Sud 11, Villejuif, France.
85
Department of Computer Languages and Systems, University Jaume I, Castellon, Spain.
86
INSERM U1167, Institut Pasteur de Lille, University of Lille, Lille, France.
87
INSERM U995, Hôpital Jeanne de Flandre, CHU-Lille, University of Lille, Lille, France.
88
Paavo Nurmi Centre, Sports and Exercise Medicine Unit, Department of Physical Activity and Health, Turku, Finland.
89
Department of Pediatrics, Turku University Hospital, Turku, Finland.
90
Department of Physiology, University of Turku, Turku, Finland.
91
Australian Centre for Precision Health, University of South Australia Cancer Research Institute, University of South Australia, Adelaide, Australia.
92
South Australian Health and Medical Research Institute, Adelaide, Australia.
93
Synlab Academy, Synlab Holding Deutschland GmbH, Mannheim, Germany.
94
Clinical Institute of Medical and Chemical Laboratory Diagnostics Medical University of Graz, Graz, Austria.
95
Victoria University of Wellington, Wellington, New Zealand.
96
Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore.
97
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
98
Health Services and Systems Research, Duke-NUS Medical School, Singapore.
99
Department of Genetics, University of North Carolina, Chapel Hill.
100
Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Crawley, Western Australia, Australia.
101
Department of Neonatology and Neonatal Intensive Care, The Children's Memorial Health Institute, Al. Dzieci Polskich 20, Warsaw, Poland.
102
Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD) King Abdulaziz University, Jeddah, Saudi Arabia.
103
Biomedical and Nutritional Sciences, University of Massachusetts, Lowell.
104
INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, Paris, France.
105
University of Paris Diderot, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers, Paris, France.
106
Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1138, Centre de Recherche des Cordeliers, Paris, France.
107
Department of Internal Medicine, Hospital Clinic, IDIBAPS, Barcelona, Spain.
108
Department of Epidemiology and Population Genetics, Centro Nacional Investigación, Cardiovasculares (CNIC), Madrid, Spain.
109
College of Public Health, University of Kentucky, Lexington.
110
Department of Statistics and Applied Probability, Faculty of Science, National University of Singapore, Singapore.
111
Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, Netherlands.
112
Friedman School of Nutrition Science & Policy, Tufts University, Boston, Massachusetts.
113
Department of Epidemiology, University of Washington, Seattle.
114
Department of Health Sciences, University of Washington, Seattle.
115
Kaiser Permanent Washington Health Research Institute, Seattle.
116
Carolina Center for Genome Sciences, University of North Carolina, Chapel Hill.

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.

Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center