PDF(Pubmed)
Abstract：
UNASSIGNED: To the best of our knowledge, numerous observational studies have linked pregnancy complications to increased risks of diabetes and cardiovascular disease (CVD), causal evidence remains lacking. Our aim was to estimate the association of adverse pregnancy outcomes with diabetes and cardiovascular diseases.
UNASSIGNED: A two-sample Mendelian randomization (MR) analysis was employed, which is not subject to potential reverse causality. Data for pregnancy complications were obtained from the FinnGen consortium. For primary analysis, outcome data on diabetes, related traits, stroke, and coronary heart disease (CHD) were extracted from the GWAS Catalog, MAGIC, MEGASTROKE, and CARDIoGRAMplusC4D consortium. The MAGIC and UKB consortium datasets were used for replication and meta-analysis. Causal effects were appraised using inverse variance weighted (IVW), weighted median (WM), and MR-Egger. Sensitivity analyses were implemented with Cochran\'s Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out (LOO) analysis and the funnel plot.
UNASSIGNED: Genetically predicted gestational diabetes mellitus (GDM) was causally associated with an increased diabetes risk (OR=1.01, 95% CI=1-1.01, P<0.0001), yet correlated with lower 2-hour post-challenge glucose levels (OR=0.89, 95% CI=0.82-0.97, P=0.006). Genetic liability for pregnancy with abortive outcomes indicated decreased fasting insulin levels (OR=0.97, 95% CI=0.95-0.99, P=0.02), but potentially elevated glycated hemoglobin levels (OR=1.02, 95% CI=1.01-1.04, P=0.01). Additionally, hypertensive disorders in pregnancy was tentatively linked to increased risks of stroke (OR=1.11, 95% CI=1.04-1.18, P=0.002) and CHD (OR=1.3, 95% CI=1.2-1.4, P=3.11E-11). Gestational hypertension might have a potential causal association with CHD (OR=1.11, 95% CI=1.01-1.22, P=0.04). No causal associations were observed between preterm birth and diabetes, stroke, or CHD.
UNASSIGNED: The findings of this study provide genetic evidence that gestational diabetes, pregnancy with abortive outcomes, and hypertensive disorders in pregnancy may serve as early indicators for metabolic and cardiovascular risks. These insights are pivotal for the development of targeted screening and preventive strategies.
UNASSIGNED: A two-sample Mendelian randomization (MR) analysis was employed, which is not subject to potential reverse causality. Data for pregnancy complications were obtained from the FinnGen consortium. For primary analysis, outcome data on diabetes, related traits, stroke, and coronary heart disease (CHD) were extracted from the GWAS Catalog, MAGIC, MEGASTROKE, and CARDIoGRAMplusC4D consortium. The MAGIC and UKB consortium datasets were used for replication and meta-analysis. Causal effects were appraised using inverse variance weighted (IVW), weighted median (WM), and MR-Egger. Sensitivity analyses were implemented with Cochran\'s Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out (LOO) analysis and the funnel plot.
UNASSIGNED: Genetically predicted gestational diabetes mellitus (GDM) was causally associated with an increased diabetes risk (OR=1.01, 95% CI=1-1.01, P<0.0001), yet correlated with lower 2-hour post-challenge glucose levels (OR=0.89, 95% CI=0.82-0.97, P=0.006). Genetic liability for pregnancy with abortive outcomes indicated decreased fasting insulin levels (OR=0.97, 95% CI=0.95-0.99, P=0.02), but potentially elevated glycated hemoglobin levels (OR=1.02, 95% CI=1.01-1.04, P=0.01). Additionally, hypertensive disorders in pregnancy was tentatively linked to increased risks of stroke (OR=1.11, 95% CI=1.04-1.18, P=0.002) and CHD (OR=1.3, 95% CI=1.2-1.4, P=3.11E-11). Gestational hypertension might have a potential causal association with CHD (OR=1.11, 95% CI=1.01-1.22, P=0.04). No causal associations were observed between preterm birth and diabetes, stroke, or CHD.
UNASSIGNED: The findings of this study provide genetic evidence that gestational diabetes, pregnancy with abortive outcomes, and hypertensive disorders in pregnancy may serve as early indicators for metabolic and cardiovascular risks. These insights are pivotal for the development of targeted screening and preventive strategies.
摘要：
■据我们所知,许多观察性研究将妊娠并发症与糖尿病和心血管疾病（CVD）的风险增加联系起来，因果证据仍然缺乏。我们的目的是评估不良妊娠结局与糖尿病和心血管疾病的关系。
■采用双样本孟德尔随机化（MR）分析，不受潜在反向因果关系的影响。妊娠并发症的数据来自FinnGen联盟。对于主要分析，糖尿病结局数据，相关性状，中风,和冠心病（CHD）从GWAS目录中提取，魔术,巨大的胃,和CARDIOGRAMplusC4D联盟。MAGIC和UKB联盟数据集用于复制和荟萃分析。使用逆方差加权(IVW)评估因果关系，加权中位数(WM)，还有MR-Egger.用Cochran的Q检验进行灵敏度分析，MR-Egger截距测试,MR-PRESSO,留一法(LOO)分析和漏斗图。
■遗传预测的妊娠期糖尿病（GDM）与糖尿病风险增加有因果关系（OR=1.01，95％CI=1-1.01，P<0.0001），但与攻击后2小时葡萄糖水平较低相关(OR=0.89,95%CI=0.82-0.97,P=0.006).妊娠与流产结局的遗传责任表明空腹胰岛素水平降低（OR=0.97，95％CI=0.95-0.99，P=0.02），但可能升高糖化血红蛋白水平（OR=1.02，95％CI=1.01-1.04，P=0.01）。此外,妊娠期高血压疾病与卒中(OR=1.11,95%CI=1.04~1.18,P=0.002)和冠心病(OR=1.3,95%CI=1.2~1.4,P=3.11E-11)风险升高有初步关联.妊娠期高血压与冠心病可能存在潜在的因果关系(OR=1.11,95%CI=1.01~1.22,P=0.04)。没有观察到早产和糖尿病之间的因果关系，中风,或CHD。
■这项研究的结果提供了遗传证据，表明妊娠期糖尿病，怀孕有流产的结果，妊娠期高血压疾病可以作为代谢和心血管风险的早期指标。这些见解对于制定有针对性的筛查和预防策略至关重要。
■采用双样本孟德尔随机化（MR）分析，不受潜在反向因果关系的影响。妊娠并发症的数据来自FinnGen联盟。对于主要分析，糖尿病结局数据，相关性状，中风,和冠心病（CHD）从GWAS目录中提取，魔术,巨大的胃,和CARDIOGRAMplusC4D联盟。MAGIC和UKB联盟数据集用于复制和荟萃分析。使用逆方差加权(IVW)评估因果关系，加权中位数(WM)，还有MR-Egger.用Cochran的Q检验进行灵敏度分析，MR-Egger截距测试,MR-PRESSO,留一法(LOO)分析和漏斗图。
■遗传预测的妊娠期糖尿病（GDM）与糖尿病风险增加有因果关系（OR=1.01，95％CI=1-1.01，P<0.0001），但与攻击后2小时葡萄糖水平较低相关(OR=0.89,95%CI=0.82-0.97,P=0.006).妊娠与流产结局的遗传责任表明空腹胰岛素水平降低（OR=0.97，95％CI=0.95-0.99，P=0.02），但可能升高糖化血红蛋白水平（OR=1.02，95％CI=1.01-1.04，P=0.01）。此外,妊娠期高血压疾病与卒中(OR=1.11,95%CI=1.04~1.18,P=0.002)和冠心病(OR=1.3,95%CI=1.2~1.4,P=3.11E-11)风险升高有初步关联.妊娠期高血压与冠心病可能存在潜在的因果关系(OR=1.11,95%CI=1.01~1.22,P=0.04)。没有观察到早产和糖尿病之间的因果关系，中风,或CHD。
■这项研究的结果提供了遗传证据，表明妊娠期糖尿病，怀孕有流产的结果，妊娠期高血压疾病可以作为代谢和心血管风险的早期指标。这些见解对于制定有针对性的筛查和预防策略至关重要。
