Migraines could be genetically linked to increased CVD risk

Migraines and an increased risk of cardiovascular disease appear to be genetically linked, according to a study published this week in the journal PLOS ONE.

Lead study author Bendik S. Winsvold, MD, and a team of researchers reviewed three genome-wide association meta-analyses of migraine and coronary artery disease (CAD) to identify shared genetic risk loci in thousands of patients. Winsvold and co-first author Francesco Bettella used data from three large-scale studies in conjunction with a conditional false discovery rate approach, which has been used in previous studies to identify shared risk loci and susceptibility for diseases like schizophrenia, hypertension and Alzheimer’s disease, the authors wrote.

According to Winsvold and colleagues’ research, migraines are associated with an estimated heritability of 42 percent. The pathogenic mechanisms of the painful condition are still somewhat unknown, but migraines affect around 14 percent of the general population and are the seventh leading cause of disability worldwide.

Migraines, typically considered a neurovascular disorder, have been linked to vascular dysfunction before. Winsvold and co-authors wrote that migraine can increase a patient’s risk of having an ischemic stroke twofold, and risk of CAD isn’t far behind. Migraine patients also tend to report family history of early CAD, the study stated, pointing to a shared genetic basis.

The genetic loci associated with migraine are also enriched for genes expressed in vascular and smooth muscle tissues, the authors wrote, further supporting their hypothesis.

After analyzing data from a total of 59,773 subjects, all of whom either suffered from CAD or migraines, the researchers identified three loci that showed significant cross-phenotype association, “in excess of what would be expected by chance.” All three loci were intragenic, and two had already been identified as cross-phenotype loci in prior studies.

One loci, though, was new, adding a novel element to existing research.

“From epidemiological studies there is a known comorbidity between migraine and both cervical artery dissection and CAD,” Winsvold and colleagues wrote. “It is intriguing that some of the same genetic variants seem to be involved in all three disorders, but with partly opposite effect directions.”

One of the previously discovered loci, found in the PHACTR1 gene, represents the “strongest shared risk locus” of the study, the researchers stated. The protein product of PHACTR1, Phosphatase and Actin Regulator 1 protein, is highly expressed in the brain and arteries, and has a role in the regulation of endothelial function. It’s also associated with altered vasomotor tone, according to the study.

“The results reaffirm previous reports, in addition to suggesting a novel shared risk locus in (gene) KCNK5,” the authors wrote. “A better understanding of the biological mechanisms underpinning shared genetic risk loci may improve our understanding of pathogenic mechanisms and shed light on vascular mechanisms in migraine.”