People who have a certain CLOCK gene variant are more prone to migraines when under financial strain. This study is presented at the ECNP conference in Paris and marks the first time that the genetics of circadian rhythms has been demonstrated to affect migraine.
One billion individuals worldwide suffer from migraines, a severe and incapacitating neurological condition. Migraine has been estimated to cause a financial cost of around €27 billion every year in the European Union, and $17 billion every year in the USA. In the UK, 1 in 4 women and 1 in 12 men are migraine sufferers.
The underlying causes of migraine are extremely complex, involving many genes, how they interact with environmental factors, and how different pathways in the central nervous system are involved.
It was thought it would be interesting to determine if variations of circadian genes (which affect how the body manages and responds to environmental changes, such as changes in light), were related to migraine.
The group of researchers from Hungary and the UK checked 999 patients from Budapest and 1350 from Manchester, for two variants (single nucleotide polymorphisms, SNPs) of the CLOCK gene, and how these are associated with migraine.
The CLOCK gene plays a crucial part in controlling the body’s rhythmic rhythms, such as the temperature or level of cortisol, the main stress hormone. They discovered that there was no conclusive evidence of a direct relationship between the gene and migraine, but when they took into account stress (financial stress, as determined by a financial questionnaire), they found that the examined gene variants significantly increased the likelihood of experiencing migraine-like headaches in people who were experiencing financial hardship by about 20%.
This is a really interesting study on the interaction of genetics with stress in migraine. The studied gene is involved in the circadian system, which has previously been shown to be implicated in mental disorders such as bipolar disorder, which intriguingly is comorbid with migraine. Thus, this study might provide a clue how these diseases might be linked on the genetic level which is interesting as such. But even beyond this, the study demonstrates how an environmental risk factor exerts its effect only in the presence of a given genetic risk factor. This has not been done to a great extent in migraine, making this study an exciting new lead.
Professor Andreas Reif
The CLOCK gene’s functional single nucleotide polymorphisms, which can affect how much protein is translated from the gene, were the subject of the study. Because this protein regulates the biological clock, its variations may interfere with mechanisms that help people avoid migraines when under stress.
Researcher Daniel Baksa (Semmelweis University, Budapest) said:
“This work does not show what causes migraine there is no single cause but it does show that both stress and genetics have an effect. In the work presented here, we were able to show that stress represented by financial hardship led to an increase in migraine in those who have a particular gene variant. What we need to do now is to see if other circadian gene variants in association with different stress factors cause the same effect.”
“The strength of our study is that we saw the same effect in two independent study groups, in Budapest and Manchester, so we think it is a real effect. The investigated gene variants are present in around 1/3 of the population, so they are common variants with small effect size. Our results shed light on one specific mechanism that may contribute to migraine. What it does mean is that for many people, the stress caused by financial worries can physically affect you. Migraine involves a huge health and financial burden each year, so any steps we can take to help patients understand their condition will be really welcome.”
Commenting, Professor Andreas Reif (University Hospital, Frankfurt) said:
“This is a really interesting study on the interaction of genetics with stress in migraine. The studied gene is involved in the circadian system, which has previously been shown to be implicated in mental disorders such as bipolar disorder, which intriguingly is comorbid with migraine. Thus, this study might provide a clue how these diseases might be linked on the genetic level which is interesting as such. But even beyond this, the study demonstrates how an environmental risk factor exerts its effect only in the presence of a given genetic risk factor. This has not been done to a great extent in migraine, making this study an exciting new lead.”
