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00925njm 22002777a 4500 dc Huang, Tao author Wang, Tiange author Zheng, Yan author Ellervik, Christina author Li, Xiang author Gao, Meng author Fang, Zhe author Chai, Jin-Fang author Ahluwalia, Tarun Veer S author Wang, Yujie author Voortman, Trudy author Noordam, Raymond author Frazier-Wood, Alexis author Scholz, Markus author Sonestedt, Emily author Akiyama, Masato author Dorajoo, Rajkumar author Zhou, Ang author Kilpeläinen, Tuomas O author Kleber, Marcus E author Crozier, Sarah R author Godfrey, Keith M author Lemaitre, Rozenn N author Felix, Janine F author Shi, Yuan author Gupta, Preeti author Khor, Chiea-Chuen author Lehtimäki, Terho author Wang, Carol A author Tiesler, Carla M T author Thiering, Elisabeth author Standl, Marie author Rzehak, Peter author Marouli, Eirini author He, Meian author Lecoeur, Cécile author Corella, Dolores author Lai, Chao-Qiang author Moreno, Luis A author Pitkänen, Niina author Boreham, Colin A author Zhang, Tao author Saw, Seang Mei author Ridker, Paul M author Graff, Mariaelisa author van Rooij, Frank J A author Uitterlinden, Andre G author Hofman, Albert author van Heemst, Diana author Rosendaal, Frits R author de Mutsert, Renée author Burkhardt, Ralph author Schulz, Christina-Alexandra author Ericson, Ulrika author Kamatani, Yoichiro author Yuan, Jian-Min author Power, Chris author Hansen, Torben author Sørensen, Thorkild I A author Tjønneland, Anne author Overvad, Kim author Delgado, Graciela author Cooper, Cyrus author Djousse, Luc author Rivadeneira, Fernando author Jameson, Karen author Zhao, Wanting author Liu, Jianjun author Lee, Nanette R author Raitakari, Olli author Kähönen, Mika author Viikari, Jorma author Grote, Veit author Langhendries, Jean-Paul author Koletzko, Berthold author Escribano, Joaquin author Verduci, Elvira author Dedoussis, George author Yu, Caizheng author Tham, Yih Chung author Lim, Blanche author Lim, Sing Hui author Froguel, Philippe author Balkau, Beverley author Fink, Nadia R author Vinding, Rebecca K author Sevelsted, Astrid author Bisgaard, Hans author Coltell, Oscar author Dallongeville, Jean author Gottrand, Frédéric author Pahkala, Katja author Niinikoski, Harri author Hyppönen, Elina author Pedersen, Oluf author März, Winfried author Inskip, Hazel author Jaddoe, Vincent W V author Dennison, Elaine author Wong, Tien Yin author Sabanayagam, Charumathi author Tai, E-Shyong author Mohlke, Karen L author Mackey, David A author Gruszfeld, Dariusz author Deloukas, Panagiotis author Tucker, Katherine L author Fumeron, Frédéric author Bønnelykke, Klaus author Rossing, Peter author Estruch, Ramon author Ordovas, Jose M author Arnett, Donna K author Meirhaeghe, Aline author Amouyel, Philippe author Cheng, Ching-Yu author Sim, Xueling author Teo, Yik Ying author van Dam, Rob M author Koh, Woon-Puay author Orho-Melander, Marju author Loeffler, Markus author Kubo, Michiaki author Thiery, Joachim author Mook-Kanamori, Dennis O author Mozaffarian, Dariush author Psaty, Bruce M author Franco, Oscar H author Wu, Tangchun author North, Kari E author Davey Smith, George author Chavarro, Jorge E author Chasman, Daniel I author Qi, Lu author 2019-09 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. JAMA Netw Open. 2019; 2(9):e1910915 10.1001/jamanetworkopen.2019.10915 2574-3805 2574-3805 JAMA network open 31539074 http://hdl.handle.net/20.500.12105/8372 Association of Birth Weight With Type 2 Diabetes and Glycemic Traits: A Mendelian Randomization Study