Investigating Shared Cardiovascular Factors and Genetic Overlap of Pregnancy-Related Disorders, Major Depressive Disorder, and Alzheimer’s Disease

作者：Hannah Oppenheimer, Alexey Shadrin, Jonas Ø. Andersen, Louise S. Schindler, Arielle Crestol, Ole A. Andreassen, Lars T. Westlye, Ann‐Marie G. de Lange, Dennis van der Meer, Cláudia Barth · 发表于：Biological Psychiatry · 年份：2025 · DOI：10.1016/j.biopsych.2025.09.018 · 被引用次数：2 · 研究领域：Maternal Mental Health During Pregnancy and Postpartum、Gestational Diabetes Research and Management、Pregnancy and preeclampsia studies

BACKGROUND: Pregnancy-related disorders, such as hypertensive disorders of pregnancy (HDPs) and postpartum depression, have consequences for maternal health, increasing risk for major depressive disorder (MDD) and Alzheimer's disease (AD). Observational studies show intertwined pathophysiologies and shared cardiovascular factors. However, genetic links of cardiovascular factors with pregnancy-related disorders, MDD, and AD, as well as the genetic mechanisms between the disorders, have not been fully established. METHODS: Using summary statistics from female-specific genome-wide association studies, we estimated genetic correlations and causal associations, using Mendelian randomization, between cardiovascular factors (C-reactive protein, high-density lipoprotein [HDL] cholesterol, low-density lipoprotein [LDL] cholesterol, and triglycerides), pregnancy-related disorders (HDPs and postpartum depression), MDD, and AD. For significant associations, body mass index (BMI), as a known confounder, was included in multivariable Mendelian randomization analyses. Furthermore, we applied causal mixture models (MiXeR) to explore polygenic overlap between pregnancy-related disorders, MDD, and BMI. RESULTS: We found widespread genetic correlations between cardiovascular factors, pregnancy-related disorders, and MDD. Using Mendelian randomization, higher triglycerides and lower HDL cholesterol were causally linked to higher HDP risk, and higher LDL cholesterol was linked to higher AD risk. ...