Association between brain structures and migraine: A bidirectional Mendelian randomization study

Guo, Xiaoming; Wang, Dingkun; Ying, Caidi; Hong, Yuan

doi:10.3389/fnins.2023.1148458

Cited by 11 publications

(6 citation statements)

References 49 publications

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“…Using the GWAS of longitudinal brain measures from MRI data [28], we found that migraine caused faster atrophy of the total cortical surface area and thalamic volume. These associations were not found in previous MR studies using the GWAS of cross-sectional brain measures, (42)(43) suggesting that migraine may not cause a fixed level of brain atrophy that is independent of the aging process, but rather affect the rate and pattern of brain atrophy that occurs as a person ages. We found causal effects of migraine on annual atrophy of the cortical surface area, but not on cortical volume and thickness.…”

Section: Discussioncontrasting

confidence: 68%

“…Two recent MR studies have explored the causal effects of migraine on brain measures, ( 42 – 43 ) but the GWAS data in these studies only assessed the genetic contributions to cross-sectional variations in brain structures. Using the GWAS of longitudinal brain measures from MRI data [ 28 ], we found that migraine caused faster atrophy of the total cortical surface area and thalamic volume.…”

Section: Discussionmentioning

confidence: 99%

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Genetic evidence for the causal relationships between migraine, dementia, and longitudinal brain atrophy

Zhao,

Tang,

et al. 2024

J Headache Pain

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Background Migraine is a neurological disease with a significant genetic component and is characterized by recurrent and prolonged episodes of headache. Previous epidemiological studies have reported a higher risk of dementia in migraine patients. Neuroimaging studies have also shown structural brain atrophy in regions that are common to migraine and dementia. However, these studies are observational and cannot establish causality. The present study aims to explore the genetic causal relationship between migraine and dementia, as well as the mediation roles of brain structural changes in this association using Mendelian randomization (MR). Methods We collected the genome-wide association study (GWAS) summary statistics of migraine and its two subtypes, as well as four common types of dementia, including Alzheimer’s disease (AD), vascular dementia, frontotemporal dementia, and Lewy body dementia. In addition, we collected the GWAS summary statistics of seven longitudinal brain measures that characterize brain structural alterations with age. Using these GWAS, we performed Two-sample MR analyses to investigate the causal effects of migraine and its two subtypes on dementia and brain structural changes. To explore the possible mediation of brain structural changes between migraine and dementia, we conducted a two-step MR mediation analysis. Results The MR analysis demonstrated a significant association between genetically predicted migraine and an increased risk of AD (OR = 1.097, 95% CI = [1.040, 1.158], p = 7.03 × 10− 4). Moreover, migraine significantly accelerated annual atrophy of the total cortical surface area (-65.588 cm2 per year, 95% CI = [-103.112, -28.064], p = 6.13 × 10− 4) and thalamic volume (-9.507 cm3 per year, 95% CI = [-15.512, -3.502], p = 1.91 × 10− 3). The migraine without aura (MO) subtype increased the risk of AD (OR = 1.091, 95% CI = [1.059, 1.123], p = 6.95 × 10− 9) and accelerated annual atrophy of the total cortical surface area (-31.401 cm2 per year, 95% CI = [-43.990, -18.811], p = 1.02 × 10− 6). The two-step MR mediation analysis revealed that thalamic atrophy partly mediated the causal effect of migraine on AD, accounting for 28.2% of the total effect. Discussion This comprehensive MR study provided genetic evidence for the causal effect of migraine on AD and identified longitudinal thalamic atrophy as a potential mediator in this association. These findings may inform brain intervention targets to prevent AD risk in migraine patients.

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Section: Discussioncontrasting

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Genetic evidence for the causal relationships between migraine, dementia, and longitudinal brain atrophy

Zhao,

Tang,

et al. 2024

J Headache Pain

View full text Add to dashboard Cite

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“…The results of some studies have been inconsistent, and some studies have even found an association between the use of β-adrenergic receptor blockers and an increased risk of cancer. [29][30][31] Therefore, more research is needed to clarify the effect of β-adrenergic receptor blockers on cancer risk.…”

Section: Discussionmentioning

confidence: 99%

Exploring the causal relationship between antihypertensive drugs and glioblastoma by combining drug target Mendelian randomization study, eQTL colocalization, and single‐cell RNA sequencing

Zhao,

Xie,

Ding

et al. 2024

Environmental Toxicology

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Recent reports indicate a potential oncogenic role of antihypertensive drugs in common cancers. However, it remains uncertain whether this phenomenon influences the risk of glioblastoma multiforme (GBM). This study aimed to assess the potential causal effects of blood pressure (BP) and antihypertensive drugs on GBM. Genome‐wide association study (GWAS) summary statistics for systolic blood pressure (SBP), diastolic blood pressure (DBP), and GBM in Europeans were downloaded. To represent the effects of antihypertensive drugs, we utilized single nucleotide polymorphisms (SNPs) associated with SBP/DBP adjacent to the coding regions of different antihypertensive drugs as instrumental variables to model five antihypertensive drugs, including angiotensin‐converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, β‐receptor blockers (BBs), and thiazide diuretics. Positive control studies were performed using GWAS data in chronic heart failure. The primary method for causality estimation was the inverse‐variance‐weighted method. Mendelian randomization analysis showed that BBs with the β1‐adrenergic receptor (ADRB1) as a therapeutic target could significantly reduce the risk of GBM by mediating DBP (OR = 0.431, 95% CI: 0.267–0.697, p < .001) and that they could also significantly reduce the risk of GBM by mediating SBP (OR = 0.595, 95% CI: 0.422–0.837, p = .003). Sensitivity analysis and colocalization analysis reinforced the robustness of these findings. Finally, the low expression of the ADRB1 gene in malignant gliomas was found by GBM data from TCGA and single‐cell RNA sequencing, which most likely contributed to the poor prognosis of GBM patients. In summary, our study provides preliminary evidence of some causal relationship between ADRB1‐targeted BBs and glioblastoma development. However, more studies are needed to validate these findings and further reveal the complex relationship between BP and GBM.

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“…To determine whether IVs have unbalanced pleiotropic effects that lead to bias, we performed the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) method and MR-Egger regression intercept. We calculated the intercept of the MR-Egger regression, and P > 0.05 suggested the presence of horizontal pleiotropy [ 28 ]. MR-PRESSO is based on the IVW regression framework and detects horizontally ambiguous IVs as outliers in regression [ 29 ].…”

Section: Methodsmentioning

confidence: 99%

Assessing the Causal Relationship between Genetically Determined Inflammatory Cytokines and Parkinson’s Disease Risk: A Bidirectional Two-Sample Mendelian Randomization Study

Xue,

Luo,

Chen

et al. 2024

Journal of Immunology Research

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Background. Observational studies have suggested an association between inflammatory cytokines and Parkinson’s disease (PD). This Mendelian randomization (MR) was conducted to further assess the causal correlations between inflammatory cytokines and PD. Methods. Genetic instruments associated with inflammatory cytokines were extracted from a large summary genome-wide association studies (GWAS) involving 8,293 European participants. Summary-level statistics for PD were obtained from a large-sample GWAS containing 17 studies that involved European participants. Causalities of exposures and outcomes were explored mainly using inverse variance weighted (IVW) method. Results. The IVW method indicated that basic fibroblast growth factor (FGFBasic), interleukin-2 (IL-2), and macrophage migration inhibitory factor (MIF) may be suggestively associated with the risk of PD (OR: 0.71, 95%CI: 0.52–0.96, P = 0.027; OR: 1.18, 95%CI: 1.01–1.38, P = 0.041; and OR: 1.23, 95%CI: 1.04–1.46, P = 0.018). In the reverse direction, monokine induced by interferon gamma (MIG), beta nerve growth factor (bNGF), interleukin-17 (IL-17), and interferon gamma (IFNg) are suggested to be the consequences of PD. Conclusion. Our MR analysis indicated that suggestive associations between circulating levels of FGFBasic, IL-2, and MIF and PD risk. In addition, MIG, bNGF, IL-17, and IFNg are more likely to be involved in the development of downstream PD.

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Association between brain structures and migraine: A bidirectional Mendelian randomization study

Cited by 11 publications

References 49 publications

Genetic evidence for the causal relationships between migraine, dementia, and longitudinal brain atrophy

Genetic evidence for the causal relationships between migraine, dementia, and longitudinal brain atrophy

Exploring the causal relationship between antihypertensive drugs and glioblastoma by combining drug target Mendelian randomization study, eQTL colocalization, and single‐cell RNA sequencing

Assessing the Causal Relationship between Genetically Determined Inflammatory Cytokines and Parkinson’s Disease Risk: A Bidirectional Two-Sample Mendelian Randomization Study

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