A candidate gene association study of 77 polymorphisms in migraine

J Pain. 2009 Jul;10(7):759-66. doi: 10.1016/j.jpain.2009.01.326.


Population-based studies have established an association between migraine and cardiovascular disease (CVD). We sought to investigate whether genetic variants implicated in CVD are associated with migraine. We performed an association study among 25,713 women participating in the Women's Health Study, with information on 77 previously characterized polymorphisms. Migraine and migraine aura status were self-reported. We used logistic regression to investigate the genotype-migraine association. At baseline, 4705 (18.3%) women reported history of migraine; 39.6% of the 3306 women with active migraine indicated aura. Regarding any history of migraine, the multivariable-adjusted odds ratios (95% confidence intervals) for TNF rs673 were 0.52 (0.30 to 0.89), for TGFB1 rs1800469 0.93 (0.89 to 0.98), and for CCR2 rs1799864 1.12 (1.03 to 1.21). Among active migraine with aura, the odds ratios (95% confidence intervals) were 1.35 (1.0 to 1.81) for TNF rs1800750, 1.13 (1.02 to 1.26) for TNF rs1800629, and 1.22 (1.07 to 1.40) for CCR2 rs1799864; among active migraine without aura, 0.9 (0.84 to 0.97) for TGFB1 rs1800469, 1.13 (1.01 to 1.27) for NOS3 rs3918226, and 1.12 (1.02 to 1.24) for IL9 rs2069885. After correction for multiple testing using the false discovery rate, none of the results remained significant. Our data suggest an association of polymorphisms implicated in inflammatory pathways and migraine in women. TNF, CCR2, TGFB1, NOS3, and IL9 warrant further investigation.

Perspective: This article presents results from an association study of 77 polymorphisms, implicated in CVD, and migraine. Variants in TNF, CCR2, TGFB1, NOS3, and IL9 were found to be associated with migraine but did not remain significant after adjustment for multiple testing. Variations in these genes warrant further investigation.

Publication types

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

MeSH terms

  • Female
  • Gene Frequency
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Interleukin-9 / genetics
  • Logistic Models
  • Migraine Disorders / genetics*
  • Nitric Oxide Synthase Type III / genetics
  • Odds Ratio
  • Polymorphism, Genetic*
  • Receptors, CCR2 / genetics
  • Transforming Growth Factor beta1 / genetics
  • Tumor Necrosis Factor-alpha / genetics


  • CCR2 protein, human
  • IL9 protein, human
  • Interleukin-9
  • Receptors, CCR2
  • TGFB1 protein, human
  • TNF protein, human
  • Transforming Growth Factor beta1
  • Tumor Necrosis Factor-alpha
  • NOS3 protein, human
  • Nitric Oxide Synthase Type III