Abstract
Background: Observational studies have illustrated that maternal central obesity is associated with birth size,including of birth weight, birth length and head circumference, but the causal nature of these associations remains unclear. Objective: To test the causal effect of maternal central obesity on birth size and puberty height growth using a Mendelian randomization (MR) analysis. Methods: We performed two-sample MR using summary-level genome-wide public data from the Genetic Investigation of Anthropometric Traits (GIANT) Consortium and the Early Growth Genetics Consortium (EGG). Thirty-five single nucleotide polymorphisms (SNPs), 25 SNPs and 41SNPs were selected as instrumental variables for waist-to-hip ratio adjust BMI (WHRadjBMI), waist circumference adjust BMI (WCadjBMI) and hip circumference adjust BMI (HIPadjBMI), respectively to test the causal effects of maternal central obesity on birth size and puberty height using an inverse-variance-weighted approach. Results: In this MR analysis, we found no evidence between genetic instrumental variables for waist circumference (WC)or waist-to-hip ratio (WHR) and the outcomes. We observed one standard deviation (SD) increase in hip circumference (HC) was associated with a 0.392 SD increase in birth length (p=1.1×10-6) and a 0.168 SD increase in birth weight (p=7.1×10-5), respectively.In addition, higher genetically predicted maternal HP was strongly associated with the puberty heights (0.835 SD, p=8.4×10-10). However,HP was not associated with head circumference(p=0.172). Conclusion: A genetic predisposition to higher maternal HC was causally associated with larger offspring birth weight,higher birth length, and puberty height independent of maternal BMI. However, we found no evidence of a causal association between maternal WC, WHR and birth size. Disclosure T. Huang: None. T. Geng: None.
Highlights
Observational studies have illustrated that maternal central obesity is associated with birth size, including of birth weight, birth length and head circumference, but the causal nature of these associations remains unclear
The genetic variants used as instrumental variables (IVs) must be associated with maternal central obesity; second, the genetic variants must not be associated with any confounders; third, the genetic variants must be conditionally independent of the birth size and puberty height given the maternal central obesity and confounders of the risk factor-outcome relationship
Predicted maternal central obesity Genetically predicted maternal central obesity including of waist-to-hip ratio adjusted for BMI (WHRadjBMI), waist circumference adjusted for BMI (WCadjBMI) and hip circumference adjusted for BMI (HIPadjBMI) were based on single nucleotide polymorphisms (SNPs) of genome-wide significant (P < 5 × 10− 8) from the Genetic Investigation of Anthropometric Traits (GIANT) Consortium, which have been downloaded from http://portals.broadinstitute.org/col laboration/giant/index.php/GIANT_consortium_data_files
Summary
Observational studies have illustrated that maternal central obesity is associated with birth size, including of birth weight, birth length and head circumference, but the causal nature of these associations remains unclear. Our study aimed to test the causal effect of maternal central obesity on birth size and puberty height growth using a Mendelian randomization (MR) analysis. Up to 50% of reproductive age women were overweight or obesity in Europe and the USA [1, 2]. Maternal overweight and obesity are associated with higher risks of many pregnancy complications and perinatal outcomes [3,4,5,6]. Observational studies have documented that maternal central obesity is associated with an increased risk of adverse birth outcomes [15,16,17,18]. Identifying a potential causal effect of maternal central obesity independent of BMI on birth size could clarify the causal association between maternal central
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