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Genome-Wide Analysis Identifies 86 Previously Unknown Migraine Risk Loci
A genome-wide association study (GWAS) of the 2 main migraine subtypes identified 123 risk loci, 86 of which were previously unknown. Results were published in an open-access article in Nature Genetics.
“Migraine affects over a billion individuals worldwide but its genetic underpinning remains largely unknown,” wrote Heidi Hautakangs, doctoral researcher, Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Finland, and co-authors. “Our findings[…] include new risk loci containing target genes of recent migraine drugs acting on the CGRP pathway and the serotonin 5-HT1F receptor.”
The GWAS included 102,084 migraine cases and 771,257 controls, expanding the sample size of previous meta-analyses by 71%. The meta-analysis yielded the identification of 123 migraine risk loci, including the 86 previously unknown loci.
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The researchers then used this information to assess the shared and distinct genetic components between the 2 main subtypes of migraine: migraine with aura (MA) and migraine without aura (MO). Stratification of the risk loci utilizing 29,679 cases with subtype information revealed 3 risk variants that may be specific to MA (HMOX2, CACNA1A, and MPPED2), 2 that may be specific to MO (near SPINK2 and near FECH), and 9 that raise vulnerability to migraine regardless of subtype.
Finally, the researchers observed that the migraine-associated loci tended to be embedded within both “vascular and central nervous system tissue/cell types,” thus providing strong evidence that “neurovascular mechanisms underlie migraine pathophysiology.”
“We expect that these and future GWAS data will reveal more of the heterogeneous biology of migraine and potentially point to new therapies against migraine—a leading burden for population health throughout the world,” the researchers concluded.
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