Genetic analysis for a shared biological basis between migraine and coronary artery disease

Abstract

Objective:To apply genetic analysis of genome-wide association data to study the extent and nature of a shared biological basis between migraine and coronary artery disease (CAD).Methods:Four separate methods for cross-phenotype genetic analysis were applied on data from 2 large-scale genome-wide association studies of migraine (19,981 cases, 56,667 controls) and CAD (21,076 cases, 63,014 controls). The first 2 methods quantified the extent of overlapping risk variants and assessed the load of CAD risk loci in migraineurs. Genomic regions of shared risk were then identified by analysis of covariance patterns between the 2 phenotypes and by querying known genome-wide significant loci.Results:We found a significant overlap of genetic risk loci for migraine and CAD. When stratified by migraine subtype, this was limited to migraine without aura, and the overlap was protective in that patients with migraine had a lower load of CAD risk alleles than controls. Genes indicated by 16 shared risk loci point to mechanisms with potential roles in migraine pathogenesis and CAD, including endothelial dysfunction (PHACTR1) and insulin homeostasis (GIP).Conclusions:The results suggest that shared biological processes contribute to risk of migraine and CAD, but surprisingly this commonality is restricted to migraine without aura and the impact is in opposite directions. Understanding the mechanisms underlying these processes and their opposite relationship to migraine and CAD may improve our understanding of both disorders.

Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine

“…Two separate analyses, the DEPICT and the GTEx gene expression enrichment analyses, point to vascular and smooth muscle tissues being involved in common variant susceptibility to migraine. The vascular finding is consistent with known co-morbidities and previously reported shared polygenic risk between migraine, stroke and cardiovascular diseases 67,68 . Furthermore, a recent GWA study of Cervical Artery Dissection (CeAD) identified a genome-wide significant association at the same index SNP (rs9349379 in the PHACTR1 locus) as is associated to migraine, suggesting the possibility of partially shared genetic components between migraine and CeAD 26 .…”

Migraine is associated with better cognition in the middle‐aged and elderly: the Rotterdam Study

“…Migraineurs in our study performed better in executive function and motor speed, corresponding to findings that executive function, and not memory, is inversely associated with microbleeds and stroke and CHD risk [44,45]. Such a vascular profile in migraineurs may be explained by genetically determined risk, similar to the low genetic risk for coronary artery disease demonstrated in migraineurs [46]. Additionally, cognitive differences (resulting from any physiological changes due to health-seeking behavior) may manifest only after the active migraine period, as we found better cognition in non-active migraineurs but not active migraineurs, compared with nonmigraineurs.…”

Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine

“…Two separate analyzes, the DEPICT and the GTEx gene-expression enrichment analyzes, together point to vascular and smooth muscle tissues being involved in common variant susceptibility to migraine. The vascular finding is consistent with known co-morbidities and previously reported shared polygenic risk between migraine, stroke and cardiovascular diseases 70,71 . Furthermore, a recent GWA study of Cervical Artery Dissection (CeAD) identified a genome-wide significant association at exactly the same index SNP (rs9349379) as is associated to migraine in the PHACTR1 locus, suggesting the possibility of partially shared genetic components between migraine and CeAD 30 .…”