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Genes and migraines
By Lone Frank

Most people with migraine know from their own experience that the disease runs in families. But now a group of Danish scientists at the Headache Clinic at Copenhagen’s Glostrup Hospital have carried out a study that determines just how much genetics contribute to the development of migraine. Their investigation provides a starting point for identifying the responsible genes.

Plaguing one in every eight people, migraine without aura is the most common form of migraine. With its characteristic attacks of intense pain and nausea it often interferes with every day life while representing a serious handicap for frequent sufferers. As neurologist Morten Gervil, who headed the Danish study, explains, "There is a great need to devise new and effective treatments for migraine but precious little is known about what causes the symptoms." Recently, scientists discovered that the rare form of hemiplegic familial migraine can be traced back to three distinct genetic mutations, and today there is a burgeoning interest in clarifying the genetics of the other forms of the disease.

Now the hunt for migraine genes is on

Studies of twins are the prime instrument for determining the heritability of diseases and normal traits. A pair of twins growing up together are exposed to roughly the same environment but while fraternal twins are no more genetically alike than siblings in general, identical twins share all their genes. So if a disease occurs more often in both individuals of identical pairs compared with fraternal pairs, it points to the involvement of genes. Gervil and his colleagues based the new study on clinical interviews with 947 sets of adult identical and fraternal twins. At least one twin in each pair reported suffering from migraine and all the interviewees were identified via the Danish Twin Register, in which all twins born in Denmark between 1953 and 1982 are registered. "It is often called the world’s best twin register, and it was the access to this information combined with the great interest among Danes to participate in scientific studies that made our investigation possible", says Gervil.

The patient interviews were mainly concerned with the quality and severity of symptoms, and in order to calculate the degree of heritability, the massive amounts of data were subjected to advanced computer analyses. They revealed that migraine without aura is 61 percent genetic while the remaining 39 percent can be attributed to environmental factors. Migraine, in other words, results from a combination of genes that make a person susceptible and effects from an environment that triggers and brings out the disposition. Importantly, the researcher’s analyses also suggest that the actual environmental factors are highly specific to each individual. According to Gervil, this closes the door on the long- held theory that migraine is partly a question of social inheritance, meaning that patients "learn" to get migraine headaches by growing up in a family with other migraine patients.

Now the hunt for migraine genes is on. According to Gervil it will be a tough search because a genetic factor as low as 61 percent suggests that a number of different genes are engaged in a complex interplay. Such a multi-gene mode of inheritance has also been proposed from previous family studies, and so far French and Dutch researchers have identified candidate regions on chromosomes 1 and 19. Gervil and his colleagues now join the race by investigating the genetics of a group of "their" twins and the twin’s families. "Our first step is to test if there is a link between migraine in our group of patients and the proposed candidate regions and then move on from there to look at the rest of the genome, where we hope to identify more genes involved", he says.

The Danish team is also discussing how to shed some light on the clouded involvement of the environment. Factors such as stress, red wine and onset of menstruation are known precipitators of migraine attacks and an obvious starting point would be to look more closely at the role of work-related stress and female sex hormones, says Gervil. "With information on non-genetic elements, it may be possible for individuals to prevent the disease from breaking out. However, knowledge of the genetic background will allow us to get at the underlying disease mechanisms and to develop drugs that treat not just the symptoms but the cause of migraine."

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