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Published on: June 2, 2014
Causal relationships between migraine and microstructural white matter: a Mendelian randomization study
Lei Zhao1,2, Wenhui Zhao1,2,
1CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.
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.
Insights
This study used genetic data to find causal links between brain white matter (WM) changes and migraine. Specific WM alterations, like the mode of anisotropy in the left inferior fronto-occipital fasciculus, increase migraine risk.
Area of Science:
- Neuroscience
- Genetics
- Medical Imaging
Background:
- Migraine is a disabling neurological disorder with poorly understood pathophysiology.
- Previous observational studies suggested links between white matter (WM) alterations and migraine, but lacked causal evidence.
- This study employed genetic data to investigate causal relationships between migraine and microstructural WM.
Purpose of the Study:
- To establish a causal relationship between migraine and microstructural alterations in brain white matter (WM).
- To utilize Mendelian randomization (MR) with genetic data for robust causal inference.
- To explore bidirectional causal associations between migraine and specific WM imaging-derived phenotypes (IDPs).
Main Methods:
- Conducted bidirectional two-sample Mendelian randomization (MR) analyses.
- Utilized Genome-wide association study (GWAS) summary statistics for migraine and 360 WM imaging-derived phenotypes (IDPs).
- Selected instrumental variables (IVs) from GWAS data to infer causal effects in both forward (WM on migraine) and reverse (migraine on WM) directions.
Main Results:
- Identified three significant causal associations between WM IDPs and migraine, confirmed by sensitivity analyses.
- The mode of anisotropy (MO) of the left inferior fronto-occipital fasciculus showed a causal effect on migraine (OR=1.76).
- The orientation dispersion index (OD) of the right posterior thalamic radiation causally affected migraine (OR=0.78), while migraine causally affected the OD of the left superior cerebellar peduncle (β=-0.09).
Conclusions:
- Provided genetic evidence supporting causal relationships between specific white matter microstructural alterations and migraine.
- These findings offer novel insights into the role of brain structure in migraine development and experience.
- Highlights the potential of genetic approaches like MR in understanding complex neurological disorders.
