Migrainomics — identifying brain and genetic markers of migraine

Key Points

  • Advances in neuroimaging and genetic studies have enabled substantial progress to be made towards the identification of migraine biomarkers

  • Brain function, structure and chemistry are altered in migraineurs versus healthy controls

  • Brain metrics such as functional MRI or voxel-based morphometry can be used as biomarkers of the disease state and treatment effects

  • Genetic findings have provided new evidence for the involvement of vascular mechanisms in migraine

  • Brain systems are also dependent on genetic determinants

  • A combination of genetic and imaging markers of migraine will deepen our understanding of migraine aetiology and improve our ability to prevent and treat attacks

Abstract

Migraine is one of the world's most prevalent and disabling disorders and imposes an enormous socioeconomic burden. The exact causes of migraine are unknown, and no recognizable diagnostic pathological changes have been identified. Specific identifiable markers of migraine would aid diagnosis and could provide insight into the pathogenesis of the condition, with the potential to direct development of new therapeutics. In the past few years, advances in neuroimaging and genetic studies have provided the most substantial progress towards the identification of markers. A growing number of brain imaging studies have provided important insights into the brain mechanisms that underlie migraine symptoms during and between migraine attacks. Similarly, large-scale genome-wide association studies have identified genetic variants associated with the common forms of migraine — migraine with aura and migraine without aura. In total, 44 independent single-nucleotide polymorphism loci have been robustly associated with the risk of migraine and provide new evidence for the involvement of vascular mechanisms. Both imaging and genetics, therefore, have excellent potential as markers of migraine. In this Review, we provide a summary of results regarding current and potential neuroimaging and genetic markers of migraine, consider what conclusions can be drawn from these markers about migraine mechanisms and discuss the potential of combining imaging and genetics.

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Figure 1: Development of markers of migraine states.
Figure 2: Definition of MRI measures and examples of brain function and structure in migraine.
Figure 3: Word cloud of the Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome pathways enriched in the 37 genes implicated in migraine.
Figure 4: Integrating imaging and genetics into markers of migraine.

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Acknowledgements

D.R.N. is supported in part by a National Health and Medical Research Council (NHMRC) project grant (APP1075175) and the European Union Seventh Framework Programme (2007–2013) under grant agreement no. 602633 (EUROHEADPAIN). D.B. is supported by grants from the NIH (NINDS Grants: K24NS064050, R01NS0750182, RO1 NS073977) and by the Mayday/Louis Herlands Chair for Pain Systems Science and the National Headache Foundation. L.R.G.'s migraine research is supported by NHMRC project grants APP1058808 and APP1083450.

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Correspondence to Dale R. Nyholt or David Borsook or Lyn R. Griffiths.

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D.R.N. declares no competing financial interests. L.R.G. consults for Novartis and D.B. consults for Biogen.

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Nyholt, D., Borsook, D. & Griffiths, L. Migrainomics — identifying brain and genetic markers of migraine. Nat Rev Neurol 13, 725–741 (2017). https://doi.org/10.1038/nrneurol.2017.151

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