Jeon Yaejin, Kim Ju Han
Seoul National University Biomedical Informatics (SNUBI), Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
BMC Psychiatry. 2025 Aug 6;25(1):768. doi: 10.1186/s12888-025-07152-0.
Glucagon-like peptide-1 receptor (GLP1R) agonists have gained attention for their role in diabetes treatment along with their diverse effects, such as appetite suppression, suggesting potential psychiatric benefits. This study aimed to assess the effect of GLP1R perturbation on mood disorders based on protein and biomarker levels using Mendelian randomization (MR) approach.
We conducted two-sample MR using summary statistics for GLP1R plasma levels (n = 3,301) from the INTERVAL study, glycated hemoglobin (HbA1c) levels (n = 128,610) from the Meta-Analyses of Glucose and Insulin-related traits Consortium, and bipolar disorder (BD: 371 cases/360,823 controls) and major depressive disorder (MDD: 776 cases/360,418 controls) incidences from the UK Biobank. Genetic variants associated with the plasma levels of GLP1R and HbA1c were used as proxies for the variation in GLP1R.
GLP1R level was significantly associated with a reduced risk of MDD (odds ratio [OR] = 0·9988, 95% confidence interval [CI] = 0·9978-0·9999, P = 0·0291) and of BD (OR = 0·9990, 95% CI = 0·9982-0·9998, P = 0·0182). GLP1R's HbA1c level-lowering effect was significantly associated with a decreased risk of BD (OR = 0·9786, 95% CI = 0·9613-0·9962, P = 0·0175) but not with MDD.
GLP1R perturbation may have protective effects on MDD and BD through different mechanisms, although additional clinical trials are required to determine the therapeutic implications.
Clinical trial number not applicable.
胰高血糖素样肽-1受体（GLP1R）激动剂因其在糖尿病治疗中的作用以及诸如食欲抑制等多种效应而受到关注，这表明其可能具有精神方面的益处。本研究旨在使用孟德尔随机化（MR）方法，基于蛋白质和生物标志物水平评估GLP1R扰动对情绪障碍的影响。
我们进行了两样本MR分析，使用了来自INTERVAL研究的GLP1R血浆水平（n = 3301）、来自葡萄糖和胰岛素相关性状联盟荟萃分析的糖化血红蛋白（HbA1c）水平（n = 128610）以及来自英国生物银行的双相情感障碍（BD：371例/360823例对照）和重度抑郁症（MDD：776例/360418例对照）发病率的汇总统计数据。与GLP1R和HbA1c血浆水平相关的基因变异被用作GLP1R变异的代理指标。
GLP1R水平与MDD风险降低显著相关（优势比[OR] = 0.9988，95%置信区间[CI] = 0.9978 - 0.9999，P = 0.0291），与BD风险降低也显著相关（OR = 0.9990，95% CI = 0.9982 - 0.9998，P = 0.0182）。GLP1R降低HbA1c水平作用与BD风险降低显著相关（OR = 0.9786，95% CI = 0.9613 - 0.9962，P = 0.0175），但与MDD无关。
GLP1R扰动可能通过不同机制对MDD和BD具有保护作用，尽管需要更多临床试验来确定其治疗意义。
临床试验编号不适用。
