Summary: A large new genetic study finds that many migraine-associated genes are linked to the vascular system.
Source: University of Helsinki
Many of the identified risk variants are located within or near genes that control vascular function.
The largest genetic analysis of migraine to date was published online in Nature Genetics on June 20. The meta-analysis combined DNA data from 375,000 participants across Europe, North America and Australia, including almost 60,000 individuals who experience migraine. By pooling results from 22 genome-wide association studies (GWAS), researchers discovered 38 independent genomic regions associated with migraine susceptibility, 28 of which had not been reported previously.
This international effort was led by the International Headache Genetics Consortium and included research groups from Australia, Denmark, Estonia, Finland, Germany, Iceland, the Netherlands, Norway, Spain, Sweden, the United Kingdom and the United States. Professor Aarno Palotie, who heads the consortium, emphasized the scale and collaborative nature of the project: “Our consortium is devoted to uncovering the genetic causes of migraine and during the past few years we have been able to identify many risk variants. Yet, in this latest, large-scale study, tens of new genetic risk factors were discovered. Because all of these variants modify the disease risk only slightly, the effect could only be seen when this large amount of samples became available.”
Migraine affects roughly one in seven people worldwide and remains a major cause of disability. Its molecular basis is still not fully understood, which complicates development of targeted therapies. The new genetic findings provide clearer evidence that vascular mechanisms play a significant role in migraine biology. When investigators examined the implicated genomic regions, most overlapped with known genes; notably, at least nine of these genes have prior associations with vascular disease and several others are involved in vascular tone and smooth muscle function. These results reinforce theories that vascular dysfunction contributes to migraine attacks.
Clinicians and researchers see clear practical implications. Professor John-Anker Zwart of Oslo University Hospital highlighted how genetic stratification may improve treatment development and clinical care: “These genetic findings are the first concrete step towards developing personalized, evidence-based treatments for this very complex disease. We doctors have known for a long time that migraine patients differ from each other and the drugs that work for some patients are completely inefficient for others. In the future, we hope that this information can be utilized in dividing the patients into different genetic susceptibility groups for clinical drug trials, thus increasing the chances of identifying the best possible treatment for each subgroup.”
Computational analyses played a central role in interpreting the GWAS results. Dr. Benjamin Neale from the Broad Institute noted that combining data from diverse biological databases and using novel computational methods made it possible to infer tissue-specific expression patterns and pathway enrichments even when patient tissue samples are scarce. These analyses showed a consistent enrichment of implicated genes in vascular and smooth muscle tissues, supporting a vascular contribution to migraine pathophysiology.
Source: Aarno Palotie – University of Helsinki
Image source: Adapted from the University of Helsinki press release
Original research: “Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine.” Published online June 20, 2016. DOI: 10.1038/ng.3598
Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine
This study combined genetic data from 59,674 migraine cases and 316,078 controls, identifying 44 independent single-nucleotide polymorphisms (SNPs) that reached genome-wide significance and mapped to 38 distinct genomic loci. Among these loci, 28 were novel discoveries and the analysis reported, for the first time to the authors’ knowledge, a locus on the X chromosome associated with migraine. Downstream computational and enrichment analyses indicated that many of the associated loci are linked to genes expressed in vascular tissue and smooth muscle, providing support for vascular etiologies in migraine alongside neuronal hypotheses.
This research advances understanding of migraine genetics and highlights vascular pathways as important contributors to disease risk. The discovery of multiple new susceptibility loci opens avenues for future studies aiming to translate genetic insights into targeted therapies and more personalized clinical trials.