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

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

JAMA Netw Open 2019 09 4;2(9):e1910915. Epub 2019 Sep 4.

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

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.

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Source
http://dx.doi.org/10.1001/jamanetworkopen.2019.10915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6755534PMC
September 2019
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