Migraine and Posterior Circulation Ischemic Stroke: Is There a Genetic Overlap?

Woman-migraine
Researchers sought to assess whether patients with migraine had a greater risk for PCiS than ACiS and if patients genetically predisposed to migraine showed an increased risk for PCiS or ACiS.

A genetic relationship between migraine without aura and unspecified migraine with stroke may be more significant with posterior circulation ischemic stroke (PCiS) than anterior circulation ischemic stroke (ACiS), according to study findings published in the Journal of Stroke and Cerebrovascular Diseases.

Migraine is associated with an increased risk for ischemic stroke, especially in migraine with aura. PCiS has not been assessed as an observable trait in genetic studies associating migraine and stroke. Researchers sought to investigate if individuals with migraine had a greater risk for PCiS than ACiS and if those individuals genetically predisposed to migraine showed increased risk for PCiS or ACiS.

To accomplish this, they conducted a retrospective exploratory study of 15,396 nonstroke control individuals and 464 PCiS patients (60.9±14.5 years of age; 32.3% female; 62% hypertension; 26.4% diabetes mellitus; 91.9% European ancestry) and 1079 ACiS patients (63.2±14.5 years of age; 39% female; 65.3% hypertension; 22.4% diabetes mellitus; 91.3% European ancestry). Control individuals were comparable in ancestry and genotype, however age data was unavailable for this cohort. For patients with stroke, data was gathered from the neuroimaging repository of the MRI-GENetics Interface Exploration (MRI-GENIE) collaboration.

Only clearly identifiable lesion location led to classification of PCiS or ACiS. Polygenic risk scores (PRSs) were developed for migraine with aura, migraine without aura, and any migraine for PCiS and ACiS and compared with control individuals.

Any migraine PRSs suggested increased risk for PCiS (Odds ratio [OR], 1.13-1.15; 95% CI, P =.010-.03) and decreased risk for ACiS (OR, .91-.93; 95% CI, P =.010-.039). PRSs for migraine without aura showed a stronger association with PCiS (OR, 1.12-1.15; 95% CI, P =.008-.028), but not with ACiS. Migraine PRSs were higher for any migraine in PCiS than ACiS (OR, 1.16-1.20; 95% CI, P =.001-.010) and higher in migraine without aura in PCiS than ACiS (OR, 1.25-1.26; 95% CI, P =.032-.048). No association was noted in migraine with aura PRSs.

Study limitations included selection bias, unavailability of migraine comorbidity data, and underpowered sample of stroke cases.

Researchers concluded that their findings suggest, “a stronger genetic overlap between unspecified migraine and migraine without aura with PCiS compared to ACiS. Possible shared mechanisms include dysregulation of cerebral vessel endothelial function.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

Frid P, Xu H, Mitchell BD, et al. Migraine-associated common genetic variants confer greater risk of posterior vs. anterior circulation ischemic stroke☆. J Stroke Cerebrovasc Dis. Published online May 13, 2022. doi:10.1016/j.jstrokecerebrovasdis.2022.106546