Genetically predicted body mass index and maternal outcomes of pregnancy: A two‐sample Mendelian randomisation study

医学 优势比 置信区间 体质指数 人口 混淆 产科 妊娠期糖尿病 孟德尔随机化 怀孕 内科学 人口学 遗传学 妊娠期 生物 基因型 环境卫生 遗传变异 社会学 基因
作者
Maddalena Ardissino,Miranda Geddes‐Barton,Anita Banerjee
出处
期刊:Bjog: An International Journal Of Obstetrics And Gynaecology [Wiley]
被引量:2
标识
DOI:10.1111/1471-0528.17650
摘要

Abstract Objective Observational studies have described associations between obesity and adverse outcomes of pregnancy but observational results are liable to influence by residual confounding. Mendelian randomisation (MR) leverages the ‘natural’ genetic randomisation to risk of an exposure occurring at allele assortment and conception. Similar to randomisation in a clinical trial, this limits the potential for the influence of confounding. Design A two‐sample MR study. Setting Summary statistics from published genome wide association studies (GWAS) in European ancestry populations. Population or Sample Instrumental variants for body mass index (BMI) were obtained from a study on 434 794 females. Methods Inverse‐variance weighted MR was used to assess the association between BMI and all outcomes. Sensitivity analyses with weighted median and MR‐Egger were also performed. Main outcome measures Female‐specific genetic association estimates for outcomes were extracted from the sixth round of analysis of the FINNGEN cohort data. Results Higher genetically predicted BMI was associated with higher risk of pre‐eclampsia (odds ratio [OR] per standard deviation 1.68, 95% confidence interval [CI] 1.46–1.94, P = 8.74 × 10 −13 ), gestational diabetes (OR 1.67, 95% CI 1.46–1.92, P = 5.35 × 10 −14 ), polyhydramnios (OR 1.40, 95% CI 1.00–1.96, P = 0.049). There was evidence suggestive of a potential association with higher risk of premature rupture of membranes (OR 1.16, 95% CI 1.00–1.36, P = 0.050) and postpartum depression (OR 1.12, 95% CI 0.99–1.27, P = 0.062). Conclusions Higher genetically predicted BMI is associated with marked increase in risk of pre‐eclampsia, gestational diabetes and polyhydramnios. The relation between genetically predicted BMI and premature rupture of membranes and postpartum depression should be assessed in further studies. Our study supports efforts to target BMI as a cardinal risk factor for maternal morbidity in pregnancy.
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