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The relationship between major depression and migraine: A bidirectional two-sample Mendelian randomization study

BACKGROUND: 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 bi...

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Autores principales: Lv, Xiaofeng, Xu, Bojun, Tang, Xiurong, Liu, Shanshan, Qian, Jun-Hui, Guo, Julan, Luo, Jian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10140565/
https://www.ncbi.nlm.nih.gov/pubmed/37122299
http://dx.doi.org/10.3389/fneur.2023.1143060
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author Lv, Xiaofeng
Xu, Bojun
Tang, Xiurong
Liu, Shanshan
Qian, Jun-Hui
Guo, Julan
Luo, Jian
author_facet Lv, Xiaofeng
Xu, Bojun
Tang, Xiurong
Liu, Shanshan
Qian, Jun-Hui
Guo, Julan
Luo, Jian
author_sort Lv, Xiaofeng
collection PubMed
description BACKGROUND: 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. METHODS: 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. RESULTS: Random effects IVW results were (MDD-Migraine: odds ratio (OR), 1.606, 95% confidence interval (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), 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. CONCLUSION: 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.
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spelling pubmed-101405652023-04-29 The relationship between major depression and migraine: A bidirectional two-sample Mendelian randomization study Lv, Xiaofeng Xu, Bojun Tang, Xiurong Liu, Shanshan Qian, Jun-Hui Guo, Julan Luo, Jian Front Neurol Neurology BACKGROUND: 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. METHODS: 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. RESULTS: Random effects IVW results were (MDD-Migraine: odds ratio (OR), 1.606, 95% confidence interval (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), 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. CONCLUSION: 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. Frontiers Media S.A. 2023-04-14 /pmc/articles/PMC10140565/ /pubmed/37122299 http://dx.doi.org/10.3389/fneur.2023.1143060 Text en Copyright © 2023 Lv, Xu, Tang, Liu, Qian, Guo and Luo. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neurology
Lv, Xiaofeng
Xu, Bojun
Tang, Xiurong
Liu, Shanshan
Qian, Jun-Hui
Guo, Julan
Luo, Jian
The relationship between major depression and migraine: A bidirectional two-sample Mendelian randomization study
title The relationship between major depression and migraine: A bidirectional two-sample Mendelian randomization study
title_full The relationship between major depression and migraine: A bidirectional two-sample Mendelian randomization study
title_fullStr The relationship between major depression and migraine: A bidirectional two-sample Mendelian randomization study
title_full_unstemmed The relationship between major depression and migraine: A bidirectional two-sample Mendelian randomization study
title_short The relationship between major depression and migraine: A bidirectional two-sample Mendelian randomization study
title_sort relationship between major depression and migraine: a bidirectional two-sample mendelian randomization study
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10140565/
https://www.ncbi.nlm.nih.gov/pubmed/37122299
http://dx.doi.org/10.3389/fneur.2023.1143060
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