Affiliation:
1. Department of Occupational and Environmental Health Healthy Food Evaluation Research Center, West China School of Public Health and West China Fourth Hospital, Sichuan University Chengdu China
2. Laboratory of Molecular Translational Medicine, Center for Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Department of Pediatrics West China Second University Hospital, Sichuan University Chengdu China
3. Food Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province Chengdu China
Abstract
AbstractAimTo assess the sex‐ and time‐specific causal effects of obesity‐related anthropometric traits on glycaemic traits.Materials and MethodsWe used univariate and multivariate Mendelian randomization to assess the causal associations of anthropometric traits (gestational variables, birth weight, childhood body mass index [BMI], BMI, waist‐to‐hip ratio [WHR], BMI‐adjusted WHR [WHRadjBMI]) with fasting glucose and insulin in Europeans from the Early Growth Genetics Consortium (n ≤ 298 142), the UK Biobank, the Genetic Investigation of Anthropometric Traits Consortium (n ≤ 697 734; females: n ≤ 434 794; males: n ≤ 374 754) and the Meta‐Analyses of Glucose and Insulin‐related traits Consortium (n ≤ 151 188; females: n ≤ 73 089; males: n ≤ 67 506), adjusting for maternal genetic effects, smoking, alcohol consumption, and age at menarche.ResultsWe observed a null association for gestational variables, a negative association for birth weight, and positive associations for childhood BMI and adult traits (BMI, WHR, and WHRadjBMI). In female participants, increased birth weight causally decreased fasting insulin (betaIVW, −0.07, 95% confidence interval [CI] −0.11 to −0.03; p = 1.92 × 10−3), but not glucose levels, which was annulled by adjusting for age at menarche. In male participants, increased birth weight causally decreased fasting glucose (betainverse‐variance‐weighted (IVW), −0.07, 95% CI −0.11 to −0.03; p = 3.22 × 10−4), but not insulin levels. In time‐specific analyses, independent effects of birth weight were absent in female participants, and were more pronounced in male participants. Independent effects of childhood BMI were attenuated in both sexes; independent effects of adult traits differed by sex.ConclusionsOur findings provide evidence for causal and independent effects of sex‐ and time‐specific anthropometric traits on glycaemic variables, and highlight the importance of considering multiple obesity exposures at different time points in the life course.
Funder
Science and Technology Department of Sichuan Province
Subject
Endocrinology,Endocrinology, Diabetes and Metabolism,Internal Medicine