Migraine Genetics
abstract & commentary
Source: Gervil M, et al. Migraine without aura: A population-based twin study. Ann Neurol 1999;46:606-611.
Migraine genetics has become an area of intense interest since the recent findings that familial hemiplegic migraine is caused by specific mutations at chromosomes 1 and 19. Although this represents an uncommon clinical syndrome, population-based genetic studies have been useful in tracing a genetic component for the more general condition of migraine with aura. The current population twin-based study was undertaken to examine genetic factors in migraine without aura. There were 2680 monozygotic and same-sex dizygotic twin pairs recruited from the population-based Danish Twin Registry. One of the pair of 1136 twin pairs screened positive for migraine or severe headache and was eligible. Follow-up interviews were obtained in 947 twin pairs (353 monozygotic, 594 dizygotic). The pairwise concordance rate was higher in the monozygotic (28%) than in the dizygotic (18%) twin pairs (P = 0.04). Furthermore, the probandwise concordance rate was also higher in the monozygotic (40% CI, 33-48%) compared to the dizygotic (28% CI, 23-33%) twin pairs. Gervil and associates conclude that the genetic susceptibility to migraine without aura reflects the contribution of several minor genes. The conclusion derives from the fact than the concordance rate in both monozygotic and dizygotic twin pairs is only moderate, a fact reflected by the monozygotic concordance rate of less than 50% penetrance.
Commentary
The current study is the first to demonstrate the complex genetic factors underlying migraine. Given the variable expression of migraine, genetic twin studies of this kind have been difficult to perform. This study is important not only for what it shows but how it shows it. In a condition like migraine with a general population prevalence rate of 15-20%, population-based genetic studies require meticulous methodology. Indeed, Gervil et al not only used the best twin registry in the world, but also relied on direct interview techniques using International Headache Society standard operational criteria. The 1.4 times concordance rate for migraine without aura in monozygotic compared to dizygotic twins was modest and suggests a combination of genetics and environmental factors. The fact that the dizygotic risk was similar to nontwin siblings of probands in the general population suggests that environmental factors are specific for the individual and not shared. —jr
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