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