Association of Birth Weight With Type 2 Diabetes and Glycemic Traits
Authors: Tao Huang, Tiange Wang, Yan Zheng, Christina Ellervik, Xiang Li, Meng Gao, Zhe Fang, Jin-Fang Chai, Tarun veer S. Ahluwalia, Yujie Wang, Trudy Voortman, Raymond Noordam, Alexis Frazier-Wood, Markus Scholz, Emily Sonestedt, Masato Akiyama, Rajkumar Dorajoo, Ang Zhou, Tuomas O. Kilpeläinen, Marcus E. Kleber, Sarah R. Crozier, Keith M. Godfrey, Rozenn Lemaitre, Janine F. Felix, Yuan Shi, Preeti Gupta, Chiea-Chuen Khor, Terho Lehtimäki, Carol A. Wang, Carla M. T. Tiesler, Elisabeth Thiering, Marie Standl, Peter Rzehak, Eirini Marouli, Meian He, Cécile Lecoeur, Dolores Corella, Chao-Qiang Lai, Luis A. Moreno, Niina Pitkänen, Colin A. Boreham, Tao Zhang, Seang Mei Saw, Paul M. Ridker, Mariaelisa Graff, Frank J. A. van Rooij, Andre G. Uitterlinden, Albert Hofman, Diana van Heemst, Frits R. Rosendaal, Renée de Mutsert, Ralph Burkhardt, Christina-Alexandra Schulz, Ulrika Ericson, Yoichiro Kamatani, Jian-Min Yuan, Chris Power, Torben Hansen, Thorkild I. A. Sørensen, Anne Tjønneland, Kim Overvad, Graciela Delgado, Cyrus Cooper, Luc Djousse, Fernando Rivadeneira, Karen Jameson, Wanting Zhao, Jianjun Liu, Nanette R. Lee, Olli Raitakari, Mika Kähönen, Jorma Viikari, Veit Grote, Jean-Paul Langhendries, Berthold Koletzko, Joaquin Escribano, Elvira Verduci, George Dedoussis, Caizheng Yu, Yih Chung Tham, Blanche Lim, Sing Hui Lim, Philippe Froguel, Beverley Balkau, Nadia R. Fink, Rebecca K. Vinding, Astrid Sevelsted, Hans Bisgaard, Oscar Coltell, Jean Dallongeville, Frédéric Gottrand, Katja Pahkala, Harri Niinikoski, Elina Hyppönen, Oluf Pedersen, Winfried März, Hazel Inskip, Vincent W. V. Jaddoe, Elaine Dennison, Tien Yin Wong, Charumathi Sabanayagam, E-Shyong Tai, Karen L. Mohlke, David A. Mackey, Dariusz Gruszfeld, Panagiotis Deloukas, Katherine L. Tucker, Frédéric Fumeron, Klaus Bønnelykke, Peter Rossing, Ramon Estruch, Jose M. Ordovas, Donna K. Arnett, Aline Meirhaeghe, Philippe Amouyel, Ching-Yu Cheng, Xueling Sim, Yik Ying Teo, Rob M. van Dam, Woon-Puay Koh, Marju Orho-Melander, Markus Loeffler, Michiaki Kubo, Joachim Thiery, Dennis O. Mook-Kanamori, Dariush Mozaffarian, Bruce M. Psaty, Oscar H. Franco, Tangchun Wu, Kari E. North, George Davey Smith, Jorge E. Chavarro, Daniel I. Chasman, Lu Qi
Journal: JAMA Network Open (2019)

<h3>Importance</h3> 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. <h3>Objective</h3> To test the association of birth weight with T2D and glycemic traits using a mendelian randomization analysis. <h3>Design, Setting, and Participants</h3> 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. <h3>Main Outcomes and Measures</h3> Type 2 diabetes and glycemic traits. <h3>Results</h3> 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;<i>P</i> = 4.03 × 10<sup>−5</sup>), among European participants (OR, 1.96; 95% CI, 1.42-2.71;<i>P</i> = .04), and among East Asian participants (OR, 1.39; 95% CI, 1.18-1.62;<i>P</i> = .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;<i>P</i> = .002), but not with fasting insulin, 2-hour glucose, or hemoglobin A<sub>1c</sub>concentration. <h3>Conclusions and Relevance</h3> 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.