Prenatal Environment May Impact Migraine Prevalence in Later Life

Illustration of a painful brain
3d rendered illustration of a painful brain.

Research from a large twin study carried out at the University of California (UC), San Diego suggests that the risk for developing migraine in later life is not entirely accounted for by genetic factors and may be linked to hormone exposure in the womb.

Notably, the team also recorded differences in genetic risk for migraine dependent on sex, with evidence of different genes impacting risk in women and men.

Migraine is a common neurological condition affecting more than 12% of the world’s population and causing significant disability. Those affected experience severe headaches, often on a regular basis, and women are nearly seven times more likely to experience the condition compared with men.

“Despite its prevalence, the factors that contribute to migraine are poorly understood,” said Matthew Panizzon, Ph.D., principal investigator of the study, based at the UC San Diego School of Medicine, in a press statement.

“With the data from the Swedish Twin Registry, the largest twin registry in the world, there was a unique opportunity to probe factors contributing to female-male differences in migraine.”

As reported in the journal Frontiers in Pain Research, the researchers used data from 51,872 individuals who had participated in earlier Swedish Twin Registry studies for their study. The registry is the largest of its kind and was established in the 1960s by the Karolinska Institute in Stockholm.

To investigate possible sex differences in migraine prevalence, the team used a statistical model to assess if migraine is equally heritable across men and women and also if different genes are involved in migraine in men and women.

As expected, women had a higher rate of migraine than men in the study at 17.6% vs. 5.5%, respectively. While the genetics was not explored in detail, using the relatedness of twins as a measure, migraine was found to be equally heritable in women and men. However, the researchers found some evidence to suggest “subtle evidence for differences in the genes underlying migraine across men and women.”

There was a significant 51% increase in migraine risk for women in the study with a male co-twin, compared with those with a female co-twin. The researchers think this finding could relate to the prenatal environment in the womb.

“We are the first to show that females with a male co-twin have a higher risk of migraine compared to females with a female co-twin, suggesting that prenatal factors, possibly relating to in utero hormone levels, may contribute to migraine risk,” said Morgan Fitzgerald, lead author of the study, from the University of California, San Diego School of Medicine. “We are also the first to present evidence that genetic factors related to migraine risk may be different between females and males.”

The researchers hope their findings could help researchers and clinicians understand this common condition better and ideally improve therapeutic options.

“The findings of our study are important because the more we understand the factors that contribute to migraine, and especially the differences between males and females, the more opportunity there is to improve clinical care, diagnostic abilities, and therapeutic interventions for both men and women,” concluded Panizzon.

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