Common Variant Burden Contributes to the Familial Aggregation of Migraine in 1,589 Families

Neuron. 2018 May 16;98(4):743-753.e4. doi: 10.1016/j.neuron.2018.04.014. Epub 2018 May 3.


Complex traits, including migraine, often aggregate in families, but the underlying genetic architecture behind this is not well understood. The aggregation could be explained by rare, penetrant variants that segregate according to Mendelian inheritance or by the sufficient polygenic accumulation of common variants, each with an individually small effect, or a combination of the two hypotheses. In 8,319 individuals across 1,589 migraine families, we calculated migraine polygenic risk scores (PRS) and found a significantly higher common variant burden in familial cases (n = 5,317, OR = 1.76, 95% CI = 1.71-1.81, p = 1.7 × 10-109) compared to population cases from the FINRISK cohort (n = 1,101, OR = 1.32, 95% CI = 1.25-1.38, p = 7.2 × 10-17). The PRS explained 1.6% of the phenotypic variance in the population cases and 3.5% in the familial cases (including 2.9% for migraine without aura, 5.5% for migraine with typical aura, and 8.2% for hemiplegic migraine). The results demonstrate a significant contribution of common polygenic variation to the familial aggregation of migraine.

Keywords: GWAS; PRS; disease aggregation; familial aggregation; families; genome-wide association study; hemiplegic migraine; migraine; migraine with aura; polygenic risk score.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Genetic Predisposition to Disease*
  • Genetic Variation*
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Migraine Disorders / genetics
  • Migraine with Aura / genetics*
  • Migraine without Aura / genetics*
  • Multifactorial Inheritance
  • Phenotype