Sex Differences in Migraine: A Twin Study

Migraine is a neurological disorder with a prominent sex difference such that two thirds of sufferers are female. The mechanisms behind the preponderance of migraine in women have yet to be elucidated. With data on 51,872 participants from the Swedish Twin Registry, we report results from two distinct analyses intended to clarify the degree to which genetic and environmental factors contribute to sex differences in migraine. First, we fit a sex-limitation model to determine if quantitative genetic differences (i.e., is migraine equally heritable across men and women) and/or qualitative genetic differences (i.e., are different genes involved in migraine across men and women) were present. Next, we used a multilevel logistic regression model to compare the prevalence of migraine in individuals from opposite-sex and same-sex twin pairs to determine whether differences in the prenatal hormone environment contribute to migraine risk. In the final analytic sample, women were found to have a significantly higher rate of migraine without aura relative to men (17.6% vs. 5.5%). The results from an ADE sex-limitation model indicate that migraine is equally heritable in men and women, with a broad sense heritability of 0.45, (95% CI = 0.40-0.50), while results from a reduced AE sex-limitation model provide subtle evidence for differences in the genes underlying migraine across men and women. The logistic regression analysis revealed a significant increase in migraine risk for females with a male co-twin relative to females with a female co-twin (OR = 1.51, 95% CI = 1.26-1.81). These results suggest that the prominent sex difference in migraine prevalence is not entirely accounted for by genetic factors, while demonstrating that masculinization of the prenatal environment may increase migraine risk for females. This effect points to a potential prenatal neuroendocrine factor in the development of migraine.