Abstract | AIMS: To estimate genetically predicted causal associations of general and central obesity with GDM, and to determine the mediating role of circulating lipids. METHODS: 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. RESULTS: 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. CONCLUSION: 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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Authors | Xinli Song, Cheng Wang, Tingting Wang, Senmao Zhang, Jiabi Qin |
Journal | Diabetes research and clinical practice
(Diabetes Res Clin Pract)
Vol. 197
Pg. 110561
(Mar 2023)
ISSN: 1872-8227 [Electronic] Ireland |
PMID | 36738839
(Publication Type: Journal Article)
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Copyright | Copyright © 2023 Elsevier B.V. All rights reserved. |
Topics |
- Pregnancy
- Female
- Humans
- Diabetes, Gestational
(genetics)
- Obesity, Abdominal
- Mendelian Randomization Analysis
- Genome-Wide Association Study
- Obesity
(genetics)
- Body Mass Index
- Polymorphism, Single Nucleotide
- Risk Factors
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