Migraines could be an immune system disease, opening up new treatment paths

A woman waits outside a doctor’s office to receive treatment for her migraine.
A woman waits outside a doctor’s office to receive treatment for her migraine.
Image: Lucy Nicholson | Reuters
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Current treatment for migraines is eclectic by necessity of the mystery of the disease, and includes everything from antidepressants to beta blockers to highly potent painkillers. None of it is entirely effective. It’s hard to treat a disease you don’t understand and current theories as to the elusive cause of this disease fall way short of comprehensive.

A study published this week in Nature Genetics suggests that maybe, for migraines and a number of other illnesses, we’ve been looking for causes in all the wrong places. A University of Chicago team, led by genetics researcher Andrey Rzhetsky, found that the current and widely accepted International Classification of Diseases (ICD), and other methods of classifying disease based on observable symptoms and presentations, are in fact missing important connections.

For instance, the ICD9 currently classifies migraines, which the World Health Organization estimates afflicts 17% of women and 7% of men worldwide, as a disease of the central nervous system. But Rzhetsky’s team’s approach found migraines to be much more correlated with irritable bowel syndrome (IBS) genetically, and cystitis (bladder inflammation) and urethritis (urethra inflammation), environmentally.

According to the study’s authors, this “suggest[s] that migraine is associated with general, not nervous system-specific, inflammatory processes and can possibly be mitigated with some of the treatments that have been developed for inflammatory diseases.” And since recent research indicates an immune component to both IBS and cystitis/urethritis, the study also, “suggests that migraine etiology [cause] is closely associated with immune system function and that the established disease taxonomy needs revision.”

The “genetic” and “environmental correlations” in the study don’t refer to the makeup of the diseases themselves. Rather, the findings indicate that IBS and migraines, for example, tend to both show up in people who share genetic similarities in the same patterns, suggesting a genetic correlation. Furthermore migraines and cystitis/urethritis are experienced by people in similar environments and therefore seem to be environmentally correlated. Or to put it another way, the study suggests current classification methods based solely on the symptoms of those diseases may miss correlations between any given diseases found among individuals who are either related, or live in the same household.

To perform their analysis, the researchers amassed a dataset of nearly 130,000 US families, consisting of close to half a million individuals pulled from the Truven MarketScan database; a collection of mortality and health-insurance claim data of over 240 million de-identified patients.

They analyzed that data set twice. First, they compared genetically similar people, such as parents and their children. Then, they looked at people who lived together and attempted to unspool the data to figure out what diseases seemed to correlate to a shared environment, as opposed to genetic similarity; in this case, spouses were the most valuable source of data because they tend to share very few genes.

The resulting disease “trees” revealed more than a few surprising disease correlations, but the association between migraines and IBS genetically, and migraines and cystitis/urethritis environmentally, were the among the strongest and most surprising.

There are historical corollaries to this kind of sea change in scientific thinking. For much of history, biologists relied on observations of physical and behavioral characteristics to classify plants and animals. Two specimens sharing a sufficient amount of observable characteristics and behaviors would be considered to be of the same family, if not the same species. It wasn’t until the advent, then refinement, of genetics that scientists learned that two animals can look and act in similar ways, but their connections on the evolutionary family tree may be much farther apart than appearances would suggest. For example a 2009 DNA study that focused on what was thought to be a widespread single species of Australian gecko, found at least 10 different species, each with small ranges, that hadn’t interbred in nearly 10 million years.

As to the connection between migraines and inflammatory conditions like IBS—correlation is not causation, of course. And a person could suffer from IBS, urethritis, and migraines, each for reasons having nothing to do with environment or genetics. That said, this type of analysis points to the possibility of previously hidden connections between the diseases, and that can open whole new avenues of research to pursue.