Studies of twins, spouses and familial aggregation strongly suggest that migraine without aura (MO) and migraine with aura (MA) are genetically determined. The mode of inheritance is most likely multifactorial in both MO and MA. However, autosomal dominant inheritance with reduced penetrance cannot be excluded in either MO or MA. At present the only evidence for genetic heterogeneity of MA is familial hemiplegic migraine with slowly progressive ataxia. This phenomenon can also be explained by linkage of different genes. All existing studies have been characterized by one or more of the following methodologic shortcomings: selection of probands from clinic populations, information obtained by questionnaire, family history obtained through probands, insufficient description of the attacks, lack of distinction between MO and MA. Useful strategies for future studies of migraine genetics are discussed.

The familial occurrence and mode of inheritance were analysed in families with migraine without aura (MO) and migraine with aura (MA). The probands were found among 4000 persons from the general population. All persons with MA were included as probands, and an equivalent number of probands with MO was selected as a random sample among those with MO. Spouses and first-degree relatives were blindly interviewed. All interviews were performed by one neurological research fellow. The distinct familial patterns indicate that MO and MA have a different aetiology. Compared with the general population, the first-degree relatives of probands with MO had a 1.9-fold increased risk of MO while spouses had a 1.5-fold increased risk of MO, indicating that both genetic and environmental factors are important in MO. The first-degree relatives of probands with MA had a four-fold increased risk of MA while spouses had no increased risk of MA, indicating that MA is determined largely by genetic factors. The complex segregation analysis indicate that both MO and MA have multifactorial inheritance without generational difference.

In a cross-sectional study of headache disorders in a representative general population of 1,000 persons the epidemiology of migraine with aura (MA) and migraine without aura (MO) was analysed in relation to sex and age distribution, symptomatology and precipitants. The headache disorders were classified on the basis of a clinical interview as well as a physical and a neurological examination using the operational diagnostic criteria of the International Headache Society (IHS). Lifetime prevalence of MA was 5%, male:female ratio 1:2. Lifetime prevalence of MO was 8%, M:F ratio 1:7. Women, but not men, were significantly more likely to have MO than MA. Neither MA nor MO showed correlation to age in the studied age interval (25–64 years). Premonitory symptoms occurred in 16% of subjects with MA and in 12% with MO. One or more precipitating factor was present in 61% with MA and in 90% with MO. In both MA and MO the most conspicuous precipitating factor was stress and mental tension. Visual disturbances were the most common aura phenomenon occurring in 90% of subjects with MA. Aura symptoms of sensory, motor or speech disturbances rarely occurred without coexisting visual disturbances. The pain phase of MA fulfilled the criteria for MO of the IHS. Headache was, however, less severe and shorter lasting in MA than in MO. Onset at menarche, menstrual precipitation, menstrual problems, influence of pregnancy and use of oral contraceptives all showed some relationship with the presence of MO and less with MA. The present findings suggest that MA and MO share the pain phase. Among subjects with MA and MO, 50% and 62%, respectively, had consulted their general practitioner because of migraine. Selection bias in previous clinical studies is demonstrated by comparisons with the present unselected sample.

Association with myocardial infarction and stroke is modified by cardiovascular risk status