TY - JOUR
T1 - Association of Birth Weight With Type 2 Diabetes and Glycemic Traits
T2 - A Mendelian Randomization Study
AU - Huang, Tao
AU - Wang, Tiange
AU - Zheng, Yan
AU - Ellervik, Christina
AU - Li, Xiang
AU - Gao, Meng
AU - Fang, Zhe
AU - Chai, Jin-Fang
AU - Ahluwalia, Tarun Veer S
AU - Wang, Yujie
AU - Voortman, Trudy
AU - Noordam, Raymond
AU - Frazier-Wood, Alexis
AU - Scholz, Markus
AU - Sonestedt, Emily
AU - Akiyama, Masato
AU - Dorajoo, Rajkumar
AU - Zhou, Ang
AU - Kilpeläinen, Tuomas O
AU - Kleber, Marcus E
AU - Crozier, Sarah R
AU - Godfrey, Keith M
AU - Lemaitre, Rozenn
AU - Felix, Janine F
AU - Shi, Yuan
AU - Gupta, Preeti
AU - Khor, Chiea-Chuen
AU - Lehtimäki, Terho
AU - Wang, Carol A
AU - Tiesler, Carla M T
AU - Thiering, Elisabeth
AU - Standl, Marie
AU - Rzehak, Peter
AU - Marouli, Eirini
AU - He, Meian
AU - Lecoeur, Cécile
AU - Corella, Dolores
AU - Lai, Chao-Qiang
AU - Moreno, Luis A
AU - Pitkänen, Niina
AU - Boreham, Colin A
AU - Zhang, Tao
AU - Hansen, Torben
AU - Sørensen, Thorkild I A
AU - Tjønneland, Anne
AU - Overvad, Kim
AU - Bisgaard, Hans
AU - Pedersen, Oluf
AU - Bønnelykke, Klaus
AU - Rossing, Peter
AU - BIRTH-GENE (BIG) Study Working Group
PY - 2019/9/20
Y1 - 2019/9/20
N2 - 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.
AB - 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.
U2 - 10.1001/jamanetworkopen.2019.10915
DO - 10.1001/jamanetworkopen.2019.10915
M3 - Journal article
C2 - 31539074
SN - 2574-3805
VL - 2
JO - JAMA network open
JF - JAMA network open
IS - 9
M1 - e1910915
ER -
