Research Article| Volume 197, 110561, March 2023

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Obesity and risk of gestational diabetes mellitus: A two-sample Mendelian randomization study

  • Xinli Song
    Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan, China
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  • Cheng Wang
    Department of Thoracic Surgery, The Second Xiangya Hospital of Central South University, Changsha, China
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  • Tingting Wang
    Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan, China
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  • Senmao Zhang
    Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan, China
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  • Jiabi Qin
    Corresponding author at: Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, NO. 238 Shang Ma Yuan Ling Xiang Xiangya Road, Kaifu District, Changsha, Hunan 410078, China.
    Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan, China

    National Health Committee Key Laboratory of Birth Defect for Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan, China

    Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China

    Hunan Provincial Key Laboratory of clinical epidemiology, Changsha, Hunan, China
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Published:February 02, 2023DOI:



      To estimate genetically predicted causal associations of general and central obesity with GDM, and to determine the mediating role of circulating lipids.


      Summary-level data was obtained from the largest available genome-wide association studies of five obesity traits, five lipid traits and GDM. Two-sample univariate Mendelian randomization (MR), multivariate MR, and MR-based mediation analysis was applied to determine the total effect, direct effect and the mediating effect, respectively.


      Univariate MR showed that the odds of GDM increased per 1-SD increase in body mass index (BMI) (OR = 1.64, P = 5.05 × 10−17), waist-to-hip ratio (WHR) (OR = 1.57, P = 2.27 × 10−14) and WHR adjusted for BMI (OR = 1.42, P = 6.11 × 10−15). The heterogeneous associations of waist circumference (OR = 1.64, P = 5.57 × 10−14) and hip circumference (OR = 1.20, P = 0.002) on GDM further reflected that body fat distribution could influence GDM risk. Mediation analysis suggested that triglycerides, high-density lipoprotein-cholesterol and apolipoprotein A-I each mediated between 5% and 10% of the association between obesity and GDM.


      Our findings supported a deleterious causal effect of obesity on GDM risk, where lipid metabolism acted as potential drivers of the relationships between both general and central obesity and GDM.


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