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. 2024 Jan-Dec:20:17448069241298849.
doi: 10.1177/17448069241298849.

Association between migraine and mitochondria: A Mendelian randomization study

Ming-Yang Hong  1   2 , Yu-Xin Chen  1   2 , Yi-Cheng Xiong  2 , Yi-Han Sun  3 , Abdullah Al Mamun  1   4 , Jian Xiao  1   2   4
Affiliations

Association between migraine and mitochondria: A Mendelian randomization study

Ming-Yang Hong et al. Mol Pain. 2024 Jan-Dec.

Abstract

Background and objective: Mitochondria are important organelles functioning in metabolic processes, inflammatory response and neurological disorders. Migraines are chronic and paroxysmal neurological disorders characterized by recurrent episodes of severe headache and other neurological symptoms. We explored whether mitochondria may be genetically and/or causally associated with migraine.

Methods: Summary-level statistics of mitochondrial DNA copy number (mtDNA-CN), 69 mitochondria related exposures and migraine with aura, migraine without aura, migraine with aura and triptan purchases, migraine with aura, drug-induced, migraine without aura and triptan purchases and migraine without aura, drug-induced, were collected from genome-wide association studies (GWAS). The analysis employed two-sample Mendelian randomization, utilizing various methods including MR-Egger, inverse-variance weighted (IVW), MR-PRESSO (MR-pleiotropy residual sum and outlier), maximum likelihood, and weighted median.

Results: We observed a potential association with decreased levels of mtDNA-CN with the risk of migraine without aura (Odds ratio (OR) 1.517, 95% Confidence interval (CI) 1.072-2.147, p = 0.019). Besides, for every 1 unit in NAD-dependent protein deacylase sirtuin-5 (SIRT5), relative risk of migraine without aura increased by 16.4%. For every 1 unit increase in Phenylalanine-transfer RNA (tRNA) ligase, relative risk of migraine without aura increased by 13.5%. For every 1 unit increase in Apoptosis-inducing factor 1, relative risk of migraine without aura increased by 27.4%.

Conclusion: This study indicates fresh evidence of association between mtDNA-CN, mitochondrial related exposures and migraine especially migraine without aura. The findings may shed light on developing interventions targeting on the causal pathway from mitochondria to migraine.

Keywords: Mendelian randomization; Sirtuin-5; migraine; mitochondria; mitochondrial DNA copy number; neuroinflammation.

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Conflict of interest statement

Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Mendelian randomization analysis design for assessing the causal relationship between mitochondrial DNA copy number (mtDNA-CN), 69 mitochondria-associated exposures, and migraine subtypes.
Figure 2.
Figure 2.
Forest plot to visualize the causal effect of mtDNA-CN levels on the risk of three subtypes of migraine.
Figure 3.
Figure 3.
Forest plot to visualize the causal effect of mitochondria-related exposures on the risk of migraine without aura.
Figure 4.
Figure 4.
Forest plot to visualize the causal effect of mitochondria-related exposures on the risk of migraine without aura, drug−induced.
Figure 5.
Figure 5.
Forest plot to visualize the causal effect of mitochondria-related exposures on the risk of migraine without aura and triptan purchases.
Figure 6.
Figure 6.
The tentative relationship between SIRT5, AIFM1 and migraine. By Figdraw.
See this image and copyright information in PMC

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