Identifying Genetic Connections
Genetic influence on migraine is very strong. Migraines tend to run in families, and estimates suggest that a person with a parent who has migraines has a 40 to 50 percent chance of also developing them. A person with migraines has a 70 to 80 percent chance of having a close family member (parent or sibling) who also has them.
The results can also be divided into migraine with and without aura. First degree relatives of those having migraine with aura have a chance of developing migraine with aura themselves that is four times greater than the general population. Correspondingly, such relatives of those having migraine without aura are 1.9 times more likely to develop migraine without aura.
Genetic studies suggest that multiple genes are involved in triggering migraines. A 2007 study in the journal Archives of Neurology, for example, found that three different genes — CACNA1A; ATP1A2; and SCN1A — play a role in one rare type of migraine called familial hemiplegic migraine (FHM). Since there is such variation in how migraines are experienced, as well as symptoms and triggers, it seems likely that many different genes are responsible.
Alert
A study in the journal Cephalalgia found that identical twins had higher chances of both having migraines when compared with fraternal twins. However, the rate for identical twins was not 100 percent, indicating that it is not only genetic factors that influence the development of migraine. The environment must be involved as well.
Combined Factors
It is suspected that a number of genes, working separately or together, combine to result in a lowered threshold to common migraine triggers. Future models of the genetic contribution to migraines will not only help illuminate the complex series of mechanisms through which migraines are triggered, but also help produce new therapies and prophylactic targets for migraine treatment.
Identifying Commonalities
Current research using genetically modified mice is helping researchers to pinpoint the specific mechanisms at play in migraine initiation, as well as target particular genes for intervention by new drug therapies. In the case of familial hemiplegic migraine, it appears that all three genes work together to increase the concentration of extracellular neurotransmitters in the brain. This increased concentration causes hyperexcitation of the neurons, as well as a decrease in the threshold for cortical spreading depression (CSD).
Fact
Familial hemiplegic migraine is a rare form of migraine that causes weakness in one side of the body during the aura phase. It may also be accompanied by ataxia, or gross incoordination of muscle movement. It is called familial because part of the diagnostic criteria is an immediate family history of the condition.
CSD is a known trigger of migraine aura, the precursor to many migraines. While these studies have been done only on one particular subclass of migraine, researchers believe that the results can be generalized to more common forms of migraine as well, since FHM migraines have an aura and headache that are very similar to common migraines. FHM patients and relatives are also at increased risk for normal migraines with aura, suggesting that the two types of migraine likely have some pathways in common.
In addition, the three genes implicated in the FHM study all are transporters of ions, leading researchers to believe that disruptions in ions are prevalent in FHM and normal migraines. As studies like these begin to identify the molecular basis of migraines and the metabolic pathways that are involved, researchers will gain a better understanding of the genetic basis for migraine triggers. Future preventative therapies will be able to target the specific mechanisms that trigger migraines.
