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

Y1 - 2019

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

VL - 2

JO - JAMA Network Open

JF - JAMA Network Open

SN - 2574-3805

IS - 9

M1 - e1910915

ER -