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BIRTH-GENE (BIG) Study Working Group; Huang, T; Wang, T; Zheng, Y; Ellervik, C; Li, X; Gao, M; Fang, Z; Chai, JF; Ahluwalia, TVS; Wang, Y; Voortman, T; Noordam, R; Frazier-Wood, A; Scholz, M; Sonestedt, E; Akiyama, M; Dorajoo, R; Zhou, A; Kilpeläinen, TO; Kleber, ME; Crozier, SR; Godfrey, KM; Lemaitre, R; Felix, JF; Shi, Y; Gupta, P; Khor, CC; Lehtimäki, T; Wang, CA; Tiesler, CMT; Thiering, E; Standl, M; Rzehak, P; Marouli, E; He, M; Lecoeur, C; Corella, D; Lai, CQ; Moreno, LA; Pitkänen, N; Boreham, CA; Zhang, T; Saw, SM; Ridker, PM; Graff, M; van Rooij, FJA; Uitterlinden, AG; Hofman, A; van Heemst, D; Rosendaal, FR; de Mutsert, R; Burkhardt, R; Schulz, CA; Ericson, U; Kamatani, Y; Yuan, JM; Power, C; Hansen, T; Sørensen, TIA; Tjønneland, A; Overvad, K; Delgado, G; Cooper, C; Djousse, L; Rivadeneira, F; Jameson, K; Zhao, W; Liu, J; Lee, NR; Raitakari, O; Kähönen, M; Viikari, J; Grote, V; Langhendries, JP; Koletzko, B; Escribano, J; Verduci, E; Dedoussis, G; Yu, C; Tham, YC; Lim, B; Lim, SH; Froguel, P; Balkau, B; Fink, NR; Vinding, RK; Sevelsted, A; Bisgaard, H; Coltell, O; Dallongeville, J; Gottrand, F; Pahkala, K; Niinikoski, H; Hyppönen, E; Pedersen, O; März, W; Inskip, H; Jaddoe, VWV; Dennison, E; Wong, TY; Sabanayagam, C; Tai, ES; Mohlke, KL; Mackey, DA; Gruszfeld, D; Deloukas, P; Tucker, KL; Fumeron, F; Bønnelykke, K; Rossing, P; Estruch, R; Ordovas, JM; Arnett, DK; Meirhaeghe, A; Amouyel, P; Cheng, CY; Sim, X; Teo, YY; van Dam, RM; Koh, WP; Orho-Melander, M; Loeffler, M; Kubo, M; Thiery, J; Mook-Kanamori, DO; Mozaffarian, D; Psaty, BM; Franco, OH; Wu, T; North, KE; Davey Smith, G; Chavarro, JE; Chasman, DI; Qi, L.
Association of Birth Weight With Type 2 Diabetes and Glycemic Traits: A Mendelian Randomization Study.
JAMA Netw Open. 2019; 2(9):e1910915-e1910915 Doi: 10.1001/jamanetworkopen.2019.10915 [OPEN ACCESS]
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Abstract:
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. To test the association of birth weight with T2D and glycemic traits using a mendelian randomization analysis. 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. Type 2 diabetes and glycemic traits. 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. 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.
Find related publications in this database (using NLM MeSH Indexing)
Adolescent -
Adult -
Aged -
Asian Continental Ancestry Group - genetics
Birth Weight - genetics
Blood Glucose - metabolism
Diabetes Mellitus, Type 2 - epidemiology
Diabetes Mellitus, Type 2 - genetics
European Continental Ancestry Group - genetics
European Continental Ancestry Group -
Female -
Genetic Variation -
Glycated Hemoglobin A - metabolism
Humans -
Infant, Newborn -
Insulin - metabolism
Male -
Mendelian Randomization Analysis -
Middle Aged -
Odds Ratio -
Polymorphism, Single Nucleotide -
Young Adult -

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