An international consortium of leading migraine scientists has identified over 120 regions of the genome that are connected to risk of migraine.
Migraine is a highly prevalent brain disorder that is often characterised by attacks of moderate-to-severe pulsating. It can often be associated with symptoms such as hypersensitivity to light and sound, nausea and vomiting. The lifetime prevalence of migraine is 15-20%. In addition, it is ranked the second most disabling condition in terms of years lived with disability. The prevalence of migraine is three times greater in females than in males. The two main migraine subtypes are migraine with aura (MA) and migraine without aura (MO).
The exact cause of migraine is unknown. It is believed to be a neurovascular disorder with disease mechanisms involving the brain and blood vessels. Previous research has shown that genetic factors contribute to the risk of migraine. However, it is currently unclear whether the two main subtypes share a similar genetic background.
Largest genetic study of migraine cases
To gain further insight, a recent study, published in Nature Genetics, reported the largest genome-wide association study (GWAS) meta-analysis of migraine to date. More specifically, the analysis included 102,084 migraine cases and 771,257 controls to look for genetic variants that were common in general migraine or one of the two main subtypes.
The analysis identified 123 loci of which 86 were previously unknown. The results indicated that the migraine subtypes had both shared and unique risk factors. Three risk variants appeared specific for migraine with aura (in HMOX2, CACNA1A and MPPED2), two for migraine without aura (near SPINK2 and near FECH) and nine that increased susceptibility for migraine regardless of subtype.
These risk loci included genes that encode targets for recently developed migraine-specific therapeutics, such as calcitonin gene-related peptide (CALCA/CALCB) and serotonin 1F receptor (HTR1F). Moreover, the variants were enriched in both vascular and central nervous system tissue/cell types. This supports the notion that neurovascular mechanisms underlie migraine pathophysiology.
Dr. Matti Pirinen, study lead, commented:
“These two new associations near genes that are already targeted by effective migraine drugs suggest that there could be other potential drug targets among the new genomic regions and provide a clear rationale for future genetic studies with even larger sample sizes.”
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