In the Journals

Migraine–CAD link may not have genetic basis

Previous research established an association between CAD and migraine, especially migraine with aura, but new study data suggest that gene variants may not be the cause. In fact, genetic variants shared by migraine without aura and CAD were protective against CVD, researchers reported.

“Surprisingly, when we looked for shared gene variants that might help explain part of the link between migraine and heart disease, we found no shared gene variations between migraine with aura and heart disease,” Aarno Palotie, MD, from Massachusetts General Hospital and the Broad Institute of the Massachusetts Institute of Technology and Harvard University, said in a press release. “This is surprising because the evidence is stronger that people with migraine with aura have an increased risk of heart disease than people with migraine without aura.”

Not explained by gene variants

Palotie and colleagues applied genetic analysis of genome-wide association data to determine the extent and nature of a shared biological basis between migraine and CAD. They conducted four separate methods for cross-phenotypic genetic analyses on data from genome-wide studies of migraine (19,981 cases, 56,667 controls) and CAD (21,076 cases, 63,014 controls). They quantified the extent of overlapping risk variants and assessed the load of CAD risk loci in those with migraine, and identified genomic regions of shared risk by analysis of covariance patterns between the two phenotypes and by querying known genome-wide significant loci.

According to the results, there was no association between CAD polygenic risk score and migraine with aura. High CAD polygenic risk score was associated with reduced risk for migraine without aura (P for moderate CAD risk single nucleotide polymorphism = 1.5 x 10-4; P for strong CAD risk single nucleotide polymorphism = 5.1 x 10-4).

The findings were consistent between men and women and across individual independent cohorts within the same migraine subtype, Palotie and colleagues wrote.

The researchers also found 16 loci that overlapped between migraine and CAD, indicating that possible related mechanisms include endothelial dysfunction (PHACTR1) and insulin homeostasis (GIP).

Other factors could play role

“We now need to understand why [people with migranges] who are born with a protective or neutral genetic risk profile for CAD end up with an increased risk of coronary events,” Anne Ducros, MD, PhD, from the department of neurology at Montpellier University Hospital and the University of Montpellier, France, wrote in a related editorial.

Ducros acknowledged the potential role of other genetic factors “Some rare genetic variants, which cannot be captured by the [genome-wide association study] method, could be implicated in both migraine with aura and CAD. Second, nongenetic factors could play a role. Migraine has been associated with adverse lifestyle, obesity, avoidance of physical activity, smoking, unfavorable cholesterol profiles and depression, which all increase the risk of CAD,” she wrote – by Erik Swain

Disclosure: Palotie reports serving on a genetics scientific advisory panel for Pfizer. Please see the full study for a list of all other authors’ relevant financial disclosures. Ducros reports receiving travel expenses and honoraria for an advisory board from Amgen.

Previous research established an association between CAD and migraine, especially migraine with aura, but new study data suggest that gene variants may not be the cause. In fact, genetic variants shared by migraine without aura and CAD were protective against CVD, researchers reported.

“Surprisingly, when we looked for shared gene variants that might help explain part of the link between migraine and heart disease, we found no shared gene variations between migraine with aura and heart disease,” Aarno Palotie, MD, from Massachusetts General Hospital and the Broad Institute of the Massachusetts Institute of Technology and Harvard University, said in a press release. “This is surprising because the evidence is stronger that people with migraine with aura have an increased risk of heart disease than people with migraine without aura.”

Not explained by gene variants

Palotie and colleagues applied genetic analysis of genome-wide association data to determine the extent and nature of a shared biological basis between migraine and CAD. They conducted four separate methods for cross-phenotypic genetic analyses on data from genome-wide studies of migraine (19,981 cases, 56,667 controls) and CAD (21,076 cases, 63,014 controls). They quantified the extent of overlapping risk variants and assessed the load of CAD risk loci in those with migraine, and identified genomic regions of shared risk by analysis of covariance patterns between the two phenotypes and by querying known genome-wide significant loci.

According to the results, there was no association between CAD polygenic risk score and migraine with aura. High CAD polygenic risk score was associated with reduced risk for migraine without aura (P for moderate CAD risk single nucleotide polymorphism = 1.5 x 10-4; P for strong CAD risk single nucleotide polymorphism = 5.1 x 10-4).

The findings were consistent between men and women and across individual independent cohorts within the same migraine subtype, Palotie and colleagues wrote.

The researchers also found 16 loci that overlapped between migraine and CAD, indicating that possible related mechanisms include endothelial dysfunction (PHACTR1) and insulin homeostasis (GIP).

Other factors could play role

“We now need to understand why [people with migranges] who are born with a protective or neutral genetic risk profile for CAD end up with an increased risk of coronary events,” Anne Ducros, MD, PhD, from the department of neurology at Montpellier University Hospital and the University of Montpellier, France, wrote in a related editorial.

Ducros acknowledged the potential role of other genetic factors “Some rare genetic variants, which cannot be captured by the [genome-wide association study] method, could be implicated in both migraine with aura and CAD. Second, nongenetic factors could play a role. Migraine has been associated with adverse lifestyle, obesity, avoidance of physical activity, smoking, unfavorable cholesterol profiles and depression, which all increase the risk of CAD,” she wrote – by Erik Swain

Disclosure: Palotie reports serving on a genetics scientific advisory panel for Pfizer. Please see the full study for a list of all other authors’ relevant financial disclosures. Ducros reports receiving travel expenses and honoraria for an advisory board from Amgen.