Wide-ranging Genomic Study Links Migraine-Related Genes to the Vascular System

Results from 22 genome-wide association (GWA) studies conducted by dozens of researchers worldwide suggest that migraine is linked to specific gene loci that are associated with some vascular disease or are involved in the regulation of vascular tone.

Migraine is a debilitating neurological disorder affecting around one in seven people worldwide, but its molecular mechanisms remain poorly understood. There is some debate about whether migraine is a disease of vascular dysfunction or a result of neuronal dysfunction with secondary vascular changes.

Members of the International Headache Genetics Consortium including migraine research groups from Australia, Denmark, Estonia, Finland, Germany, Iceland, the Netherlands, Norway, Spain, Sweden, the United Kingdom, and the USA carried out a major genetic study of migraine on 59,674 affected subjects and 316,078 controls from 22 GWA studies.

The investigators identified 44 independent single-nucleotide polymorphisms (SNPs) significantly associated with migraine risk that mapped to 38 distinct genomic loci, including 28 loci not previously reported and a locus that may be the first to be identified on the X chromosome. In subsequent computational analyses, the identified loci showed enrichment for genes expressed in vascular and smooth muscle tissues, consistent with a predominant theory of migraine that highlights links to the vascular system.

"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," said senior author Dr. Aarno Palotie, research director at the Institute for Molecular Medicine Finland at the University of Helsinki (Finland) and leader of the International Headache Genetics Consortium. "We simply cannot overstate the importance of international collaboration when studying genetics of complex, common diseases."

"These interesting findings linking migraine with vascular dysfunction were generated using novel computational approaches that utilize and combine data from various international biological databases. Such datasets are invaluable in situations like this when tissue samples from patients are not readily available, underscoring the importance of data sharing," said contributing author Dr. Benjamin Neale, instructor in medicine at the Harvard University Medical School (Boston, MA, USA).

The migraine genetic study was published in the June 20, 2016, online edition of the journal Nature Genetics.

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University of Helsinki
Harvard University Medical School