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.
METHODS: A two-sample MR study.
METHODS: Summary statistics from published genome wide association studies (GWAS) in European ancestry populations.
METHODS: 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.
METHODS: 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.
METHODS: A two-sample MR study.
METHODS: Summary statistics from published genome wide association studies (GWAS) in European ancestry populations.
METHODS: 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.
METHODS: 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.
摘要：
目的：观察性研究描述了肥胖与妊娠不良结局之间的关联，但观察结果容易受到残留混杂因素的影响。孟德尔随机化（MR）利用“自然”遗传随机化来评估等位基因分类和受孕时暴露的风险。类似于临床试验中的随机化，这限制了混杂因素影响的可能性。
方法：双样本MR研究。
方法：来自欧洲祖先人群中已发表的全基因组关联研究（GWAS）的汇总统计。
方法：体重指数（BMI）的仪器变体来自对434794名女性的研究。
方法：使用逆方差加权MR评估BMI与所有结局之间的关联。还进行了加权中位数和MR-Egger的敏感性分析。
方法：从对FINNGEN队列数据的第六轮分析中提取女性特异性遗传关联估计结果。
结果：较高的遗传预测BMI与较高的先兆子痫风险相关（比值比[OR]/标准差1.68，95％置信区间[CI]1.46-1.94，P=8.74×10-13），妊娠期糖尿病（OR1.67，95%CI1.46-1.92，P=5.35×10-14），羊水过多(OR1.40,95%CI1.00-1.96,P=0.049)。有证据表明与胎膜早破（OR1.16，95%CI1.00-1.36，P=0.050）和产后抑郁（OR1.12，95%CI0.99-1.27，P=0.062）的风险有潜在关联。
结论：较高的遗传预测BMI与先兆子痫的风险明显增加有关，妊娠期糖尿病和羊水过多。应在进一步的研究中评估遗传预测的BMI与胎膜早破和产后抑郁症之间的关系。我们的研究支持将BMI作为孕妇妊娠发病的主要危险因素的努力。
方法：双样本MR研究。
方法：来自欧洲祖先人群中已发表的全基因组关联研究（GWAS）的汇总统计。
方法：体重指数（BMI）的仪器变体来自对434794名女性的研究。
方法：使用逆方差加权MR评估BMI与所有结局之间的关联。还进行了加权中位数和MR-Egger的敏感性分析。
方法：从对FINNGEN队列数据的第六轮分析中提取女性特异性遗传关联估计结果。
结果：较高的遗传预测BMI与较高的先兆子痫风险相关（比值比[OR]/标准差1.68，95％置信区间[CI]1.46-1.94，P=8.74×10-13），妊娠期糖尿病（OR1.67，95%CI1.46-1.92，P=5.35×10-14），羊水过多(OR1.40,95%CI1.00-1.96,P=0.049)。有证据表明与胎膜早破（OR1.16，95%CI1.00-1.36，P=0.050）和产后抑郁（OR1.12，95%CI0.99-1.27，P=0.062）的风险有潜在关联。
结论：较高的遗传预测BMI与先兆子痫的风险明显增加有关，妊娠期糖尿病和羊水过多。应在进一步的研究中评估遗传预测的BMI与胎膜早破和产后抑郁症之间的关系。我们的研究支持将BMI作为孕妇妊娠发病的主要危险因素的努力。
