Genetic determinants of cardiovascular events among women with migraine: a genome-wide association study

PLoS One. 2011;6(7):e22106. doi: 10.1371/journal.pone.0022106. Epub 2011 Jul 14.


Background: Migraine is associated with an increased risk for cardiovascular disease (CVD). Both migraine and CVD are highly heritable. However, the genetic liability for CVD among migraineurs is unclear.

Methods: We performed a genome-wide association study for incident CVD events during 12 years of follow-up among 5,122 migraineurs participating in the population-based Women's Genome Health Study. Migraine was self-reported and CVD events were confirmed after medical records review. We calculated odds ratios (OR) and 95% confidence intervals (CI) and considered a genome-wide p-value <5×10(-8) as significant.

Results: Among the 5,122 women with migraine 164 incident CVD events occurred during follow-up. No SNP was associated with major CVD, ischemic stroke, myocardial infarction, or CVD death at the genome-wide level; however, five SNPs showed association with p<5×10(-6). Among migraineurs with aura rs7698623 in MEPE (OR = 6.37; 95% CI 3.15-12.90; p = 2.7×10(-7)) and rs4975709 in IRX4 (OR = 5.06; 95% CI 2.66-9.62; p = 7.7×10(-7)) appeared to be associated with ischemic stroke, rs2143678 located close to MDF1 with major CVD (OR = 3.05; 95% CI 1.98-4.69; p = 4.3×10(-7)), and the intergenic rs1406961 with CVD death (OR = 12.33; 95% CI 4.62-32.87; p = 5.2×10(-7)). Further, rs1047964 in BACE1 appeared to be associated with CVD death among women with any migraine (OR = 4.67; 95% CI 2.53-8.62; p = 8.0×10(-7)).

Conclusion: Our results provide some suggestion for an association of five SNPs with CVD events among women with migraine; none of the results was genome-wide significant. Four associations appeared among migraineurs with aura, two of those with ischemic stroke. Although our population is among the largest with migraine and incident CVD information, these results must be treated with caution, given the limited number of CVD events among women with migraine and the low minor allele frequencies for three of the SNPs. Our results await independent replication and should be considered hypothesis generating for future research.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid Precursor Protein Secretases / genetics
  • Aspartic Acid Endopeptidases / genetics
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / genetics*
  • Confidence Intervals
  • Extracellular Matrix Proteins / genetics
  • Female
  • Genetic Predisposition to Disease / genetics
  • Genome-Wide Association Study / methods*
  • Glycoproteins / genetics
  • Homeodomain Proteins / genetics
  • Humans
  • Migraine Disorders / genetics*
  • Myogenic Regulatory Factors / genetics
  • Odds Ratio
  • Phosphoproteins / genetics
  • Polymorphism, Single Nucleotide / genetics


  • Extracellular Matrix Proteins
  • Glycoproteins
  • Homeodomain Proteins
  • IRX4 protein, human
  • MEPE protein, human
  • Myogenic Regulatory Factors
  • Phosphoproteins
  • MDFI protein, human
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases
  • BACE1 protein, human