There has long been as association between migraine headaches and vascular (blood vessel) dysfunction of some kind, underscored by epidemiological studies and other research. New evidence for a genetic connection now comes from the analysis of several large data sets of each condition based on Genome Wide Association Studies (GWAS). GWAS have been used to compare the genomes of a large number of patients who have a particular disease with a control group not having the disease. Investigators know that scattered across human genomes are hundreds of thousands of single places in the long chain of DNA where there is a variant of one or another of the four nucleotides that make up the genetic code (A, C, T and G). These sites are called single nucleotide polymorphisms, SNPs, pronounced SNPs. What investigators s hope to find in a GWAS is that the genomes of the diseased group share certain SNPs in common, which distinguishes them from the control group. These SNPs can then serve as biomarkers of risk for the disease. Indeed, they usually are located in or near a gene involved in the disease process.
A group of Norwegian investigators* who had access to a number of independent GWAS studying SNPs associated with either chronic migraine (defined as at least 15 days a month of headaches for three months) or coronary artery disease (CAD) went the next step: They compared the SNPs found independently for the two diseases and discovered overlaps. Using complex statistical methods they further honed their search to zero in on three SNPs which turned out to be located inside genes of interest. Of this set the strongest link was to a gene that codes for phosphatase and actin regulator 1 protein. This protein is highly expressed in the brain, where it regulates synaptic activity and the forms of branches of nerve cells (dendrites). But It is also expressed in arteries where it is involved in the function of the endothelial cells lining the blood vessel walls, and in regulating the tension on the walls (called vasomotor "tone"). Investigators expect to use this kind of information as well as from the other genes of interest to shed light on pathogenic mechanisms that underlie both migraine and CAD.
*Reference: Winsvold BS, Bettella F, Witoelar A, Anttila V, Gormley P, et al. (2017) Shared genetic risk between migraine and coronary artery disease: A genome-wide analysis of common variants. PLOS ONE 12(9): e0185663. https://doi.org/10.1371/journal.pone.0185663