Lv Xiaofeng, Xu Bojun, Tang Xiurong, Liu Shanshan, Qian Jun-Hui, Guo Julan, Luo Jian
Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Front Neurol. 2023 Apr 14;14:1143060. doi: 10.3389/fneur.2023.1143060. eCollection 2023.
Previous epidemiological and other studies have shown an association between major depressive disorder (MDD) and migraine. However, the causal relationship between them remains unclear. Therefore, this study aimed to investigate the causal relationship between MDD and migraine using a bidirectional, two-sample Mendelian randomization (MR) approach.
Data on MDD and migraine, including subtypes with aura migraine (MA) and without aura migraine (MO), were gathered from a publicly available genome-wide association study (GWAS). Single nucleotide polymorphisms (SNPs) utilized as instrumental variables (IVs) were then screened by adjusting the intensity of the connection and removing linkage disequilibrium. To explore causal effects, inverse variance weighting (IVW) was used as the primary analysis method, with weighted median, MR-Egger, simple mode, and weighted mode used as supplementary analytic methods. Furthermore, heterogeneity and pleiotropy tests were carried out. Cochran's Q-test with IVW and MR-Egger was used to assess heterogeneity. Pleiotropy testing was carried out using the MR-Egger intercept and MR-PRESSO analysis methods. A leave-one-out analysis was also used to evaluate the stability of the findings. Finally, we used migraine (MA and MO) levels to deduce reverse causality with MDD risk.
Random effects IVW results were (MDD-Migraine: odds ratio (OR), 1.606, 95% confidence interval (CI), 1.324-1.949, = 1.52E-06; MDD-MA: OR, 1.400, 95%CI, 1.067-1.8378, = 0.015; MDD-MO: OR, 1.814, 95%CI, 1.277-2.578, = 0.0008), indicating a causal relationship between MDD levels and increased risk of migraine (including MA and MO). In the inverse MR analysis, the findings were all negative, while in sensitivity analyses, the results were robust except for the study of MA with MDD.
Our study confirms a causal relationship between MDD levels and increased risk of migraine, MA, and MO. There was little evidence in the reverse MR analysis to suggest a causal genetic relationship between migraine (MA and MO) and MDD risk levels.
既往的流行病学研究及其他研究表明，重度抑郁症（MDD）与偏头痛之间存在关联。然而，二者之间的因果关系仍不明确。因此，本研究旨在采用双向双样本孟德尔随机化（MR）方法，探究MDD与偏头痛之间的因果关系。
从公开的全基因组关联研究（GWAS）中收集MDD和偏头痛的数据，包括伴有先兆偏头痛（MA）和无先兆偏头痛（MO）的亚型。然后通过调整连接强度并去除连锁不平衡，筛选用作工具变量（IVs）的单核苷酸多态性（SNPs）。为探究因果效应，采用逆方差加权（IVW）作为主要分析方法，加权中位数、MR-Egger、简单模式和加权模式作为补充分析方法。此外，还进行了异质性和多效性检验。使用IVW和MR-Egger的Cochran Q检验评估异质性。采用MR-Egger截距和MR-PRESSO分析方法进行多效性检验。还采用了留一法分析来评估研究结果的稳定性。最后，我们使用偏头痛（MA和MO）水平来推断与MDD风险的反向因果关系。
随机效应IVW结果为（MDD-偏头痛：优势比（OR），1.606，95%置信区间（CI），1.324-1.949，P = 1.52E-06；MDD-MA：OR，1.400，95%CI，1.067-1.8378，P = 0.015；MDD-MO：OR，1.814，95%CI，1.277-2.578，P = 0.0008），表明MDD水平与偏头痛（包括MA和MO）风险增加之间存在因果关系。在反向MR分析中，结果均为阴性，而在敏感性分析中，除MA与MDD的研究外，结果均稳健。
我们的研究证实了MDD水平与偏头痛、MA和MO风险增加之间的因果关系。反向MR分析中几乎没有证据表明偏头痛（MA和MO）与MDD风险水平之间存在因果遗传关系。
