Elucidating the relationship between migraine risk and brain structure using genetic data

Mitchell, Brittany L.; Díaz-Torres, Santiago; Bivol, Svetlana; Cuéllar-Partida, Gabriel; Gerring, Zachary F.; Martin, Nicholas G.; Medland, Sarah E.; Grasby, Katrina L.; Nyholt, Dale R.; Rentería, Miguel E.

doi:10.1093/brain/awac105

Cited by 14 publications

(11 citation statements)

References 77 publications

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“…In addition, we used wellpowered GWAS data of migraine, which had more statistical power to detect associations than past smaller study. Finally, our results were in lined with a recent MR study based on voxel-based morphometry, which additionally increased the robustness of our results (Mitchell et al, 2022).…”

Section: Discussionsupporting

confidence: 91%

“…At the same time, observational evidence showed that HV had been negatively associated with the frequency and severity of migraine attacks (Maleki et al, 2013;Liu et al, 2017). Mitchell et al (2022) suggested that migraine attacks might influence HV in a longitudinal study. However, this reverse relationship was not verified in our study or a recent MR study.…”

Section: Discussionmentioning

confidence: 99%

“…In view of the basis that both brain morphometry and migraine risk are influenced by genetic factors, using MR analysis to improve the knowledge of the relationship between brain morphometry alterations and migraine is promising. Recently, only one MR study have investigated the association between intracranial volume and migraine (Mitchell et al, 2022). Important brain traits like cortical SA, cortical thickness, and some other traits of interests were not assessed.…”

Section: Introductionmentioning

confidence: 99%

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

Guo

Wang²,

Ying³

et al. 2023

Front. Neurosci.

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BackgroundAccumulating evidence of clinical and neuroimaging studies indicated that migraine is related to brain structural alterations. However, it is still not clear whether the associations of brain structural alterations with migraine are likely to be causal, or could be explained by reverse causality confounding.MethodsWe carried on a bidirectional Mendelian randomization analysis in order to identify the causal relationship between brain structures and migraine risk. Summary-level data and independent variants used as instruments came from large genome-wide association studies of total surface area and average thickness of cortex (33,992 participants), gray matter volume (8,428 participants), white matter hyperintensities (50,970 participants), hippocampal volume (33,536 participants), and migraine (102,084 cases and 771,257 controls).ResultsWe identified suggestive associations of the decreased surface area (OR = 0.85; 95% CI, 0.75–0.96; P = 0.007), and decreased hippocampal volume (OR = 0.74; 95% CI, 0.55–1.00; P = 0.047) with higher migraine risk. We did not find any significant association of gray matter volume, cortical thickness, or white matter hyperintensities with migraine. No evidence supporting the significant association was found in the reverse MR analysis.ConclusionWe provided suggestive evidence that surface area and hippocampal volume are causally associated with migraine risk.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Guo

Wang²,

Ying³

et al. 2023

Front. Neurosci.

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“…The GWAS-pairwise (GWAS-PW) method 77 was used to identify specific segments of the genome influencing PD and at least one of the eight brain structures with a statistically significant genetic correlation, as described previously 78 . We conducted GWAS-PW analyses for PD and each of the eight brain structures, separately.…”

Section: Methodsmentioning

confidence: 99%

Shared molecular genetic factors influence subcortical brain morphometry and Parkinson’s disease risk

García-Marín

Reyes-Pérez

Díaz-Torres

et al. 2023

npj Parkinsons Dis.

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Parkinson’s disease (PD) is a late-onset and genetically complex neurodegenerative disorder. Here we sought to identify genes and molecular pathways underlying the associations between PD and the volume of ten brain structures measured through magnetic resonance imaging (MRI) scans. We leveraged genome-wide genetic data from several cohorts, including the International Parkinson’s Disease Genomics Consortium (IPDG), the UK Biobank, the Adolescent Brain Cognitive Development (ABCD) study, the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE), the Enhancing Neuroimaging Genetics through Meta-Analyses (ENIGMA), and 23andMe. We observed significant positive genetic correlations between PD and intracranial and subcortical brain volumes. Genome-wide association studies (GWAS) - pairwise analyses identified 210 genomic segments with shared aetiology between PD and at least one of these brain structures. Pathway enrichment results highlight potential links with chronic inflammation, the hypothalamic-pituitary-adrenal pathway, mitophagy, disrupted vesicle-trafficking, calcium-dependent, and autophagic pathways. Investigations for putative causal genetic effects suggest that a larger putamen volume could influence PD risk, independently of the potential causal genetic effects of intracranial volume (ICV) on PD. Our findings suggest that genetic variants influencing larger intracranial and subcortical brain volumes, possibly during earlier stages of life, influence the risk of developing PD later in life.

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“…Large-scale genome-wide association studies (GWAS) on both brain imaging-derived phenotypes (IDPs) and neuropsychiatric disorders provide opportunities to explore the causality between exposure (e.g., brain IDPs) and outcome (e.g., diseases) [ 17 ]. Using MR, a recent study explored the causal effects of subcortical regions and intracranial volume (ICV) on migraine [ 18 ]. MR results demonstrated a possible causal relationship between smaller ICV, hippocampal and ventral diencephalon volume and increased migraine risk, while reverse MR showed causality between increased migraine risk and a larger volume of the amygdala.…”

Section: Introductionmentioning

confidence: 99%

Causal relationships between migraine and microstructural white matter: a Mendelian randomization study

Zhao

Zhao²,

Anttila³

et al. 2023

J Headache Pain

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Background Migraine is a disabling neurological disorder with the pathophysiology yet to be understood. The microstructural alteration in brain white matter (WM) has been suggested to be related to migraine in recent studies, but these evidence are observational essentially and cannot infer a causal relationship. The present study aims to reveal the causal relationship between migraine and microstructural WM using genetic data and Mendelian randomization (MR). Methods We collected the Genome-wide association study (GWAS) summary statistics of migraine (48,975 cases / 550,381 controls) and 360 WM imaging-derived phenotypes (IDPs) (31,356 samples) that were used to measure microstructural WM. Based on instrumental variables (IVs) selected from the GWAS summary statistics, we conducted bidirectional two-sample MR analyses to infer bidirectional causal associations between migraine and microstructural WM. In forward MR analysis, we inferred the causal effect of microstructural WM on migraine by reporting the odds ratio (OR) that quantified the risk change of migraine for per 1 standard deviation (SD) increase of IDPs. In reverse MR analysis, we inferred the causal effect of migraine on microstructural WM by reporting the β value that represented SDs of changes in IDPs were caused by migraine. Results Three WM IDPs showed significant causal associations (p < 3.29 × 10− 4, Bonferroni correction) with migraine and were proved to be reliable via sensitivity analysis. The mode of anisotropy (MO) of left inferior fronto-occipital fasciculus (OR = 1.76, p = 6.46 × 10− 5) and orientation dispersion index (OD) of right posterior thalamic radiation (OR = 0.78, p = 1.86 × 10− 4) exerted significant causal effects on migraine. Migraine exerted a significant causal effect on the OD of left superior cerebellar peduncle (β = − 0.09, p = 2.78 × 10− 4). Conclusions Our findings provided genetic evidence for the causal relationships between migraine and microstructural WM, bringing new insights into brain structure for the development and experience of migraine.

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Elucidating the relationship between migraine risk and brain structure using genetic data

Cited by 14 publications

References 77 publications

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

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

Shared molecular genetic factors influence subcortical brain morphometry and Parkinson’s disease risk

Causal relationships between migraine and microstructural white matter: a Mendelian randomization study

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