Epidemiological studies examine disease risk factors and differences in disease rates (i.e.
prevalence) in different populations. Genetic epidemiology determines the genetic component of a particular phenotype and its relation to environmental factors (Morton 1982). The effect by which genetic variation contributes to a phenotypic variation is defined as heritability.
Twin studies are often used to estimate heritability by comparing the correlation of a phenotype between monozygotic and dizygotic twins (Medlund et al. 1976, Kaprio 2000). If the effect of the genetic components is higher than environmental factors in disease predisposition, it may facilitate the identification of the genetic variants.
2.2.1 Prevalence
Prevalence is the proportion of a population with a disease during a particular period of time, typically either one year or life-time. The prevalence studies on the Danish and Dutch populations have shown a one-year risk of 10–16% and a life-time risk of 16–23% for migraine (Rasmussen et al. 1991, Launer et al. 1999). Similar figures were summarized in the comprehensive evaluation of headache prevalence in different populations based on the WHO's project “The Global Campaign to Reduce the Burden of Headache Worldwide”
(Stovner et al. 2007). According to this study, the global current prevalence of the IHS-based migraine is >10% in the adult population when the life-time risk for migraine is about 14%.
About two thirds of migraine patients are females in all populations, but before puberty migraine is slightly more common in boys than girls (Abu-Arefeh and Russell 1994). The urban life-style seems to correlate positively with a life-time prevalence of migraine. In Europe the prevalence of migraine is three times higher than in Africa (15% vs. 5%; Stovner et al. 2007). In Finland the number of migraine patients is estimated to be 440,000 corresponding to a population prevalence of 8% (Sillanpää et al. 2008). In contrast to common migraine, sporadic and familial hemiplegic migraine consist of only a fraction of migraine prevalence;
according to a Danish study the prevalence of hemiplegic migraine is only 0.01% (Lykke Thomsen et al. 2002).
The two main types of migraine, MA and MO, can co-occur but typically the prevalence of MA or MO is evaluated separately. The life-time prevalence of MA does not differentiate largely by gender being 8% for women and 7% for men (Russell et al. 2002). For MO the male prevalence (7%) is the same as for MA, but in females the prevalence is 19%. When the co-occurrence of MO and MA was evaluated in the clinical sample, 40% of patients were found to have both forms of attacks (Kallela et al. 2001). However, in the population-based twin sample only 6% of males and 7% of females with migraine suffered from both attacks (Ulrich et al. 1999). The difference probably originates from a selection bias; those in the clinical sample were likely more severely affected than those in the population-based twin study (Rasmussen and Stewart 2000).
2.2.2 Genetic factors
A positive family history of migraine has been reported in 37–91% of probands with migraine (Russell 1997). The epidemiological studies on twins showed two-time higher concordance rates for monozygotic (32–48%) than dizygotic (12–31%) twins suggesting genetic components in migraine susceptibility (Mulder et al. 2003). The genetic component accounts for about half (34–60%) of migraine susceptibility (Honkasalo et al. 1995, Larsson et al. 1995, Mulder et al. 2003), but population-specific variation exists. In MO the additive genetic effect is estimated to be 61% and for MA 65% (Gervil et al. 1999, Ulrich et al. 1999b).
Segregation studies on families have suggested multifactorial inheritance of both MA and MO (Russell et al. 1995), but a monogenic pattern of inheritance may be possible in some families due to a high prevalence of migraine in each generation (Russell 1997). Also, the high number of migraine-affected offspring of migraneous females has suggested a possibility of mitochondrial inheritance. The risk study on families has shown that the first degree relatives of a patient with MO have almost twice the risk of MO and 1.4-times risk for MA (Russell and Olesen 1995). However, the risk for MA has been estimated to be four times higher in the first-degree relatives of a MA patient than in the general population, but no increased risk for MO has been detected. Therefore, the migraine family risk calculations suggest that MA and MO are distinct conditions. However, in some studies no association between the migraine type (i.e. MA and MO) of a proband and type of migraine in relatives was found (Stewart et al. 1997, Nyholt et al. 2004).
2.2.3 Environmental factors
Since migraine is a complex disease, environmental factors have an important role in migraine aetiology. The most common triggering factors in migraine are occasional psychosocial, dietary, physical, environmental and hormonal factors (Scharff et al. 1995, Wöber et al. 2006), which partially explain the episodic nature of migraine. Also social factors including low education and economical status increase the incidence of migraine (Stewart et al. 1992, Lyngberg et al. 2005), but in adolescents with a family history of migraine the economical background did not seem to play role in migraine susceptibility (Bigal et al. 2007). A Swedish
study on twins showed that twins reared apart before age of three were more similar for migraine than those separated in later age (Svensson et al. 2003). Despite the low number of twins they suggested that environmental, not genetic, factors modify the difference between family members.
Between MA and MO the environmental factors seem to differentiate: A spouse of a MO patient has a significantly increased risk for MO but not for MA, but the spouse risk was missing in MA indicating higher environmental risk in MO than in MA (Russell and Olesen 1995). This was also shown in the Danish study that pointed no difference in living conditions or life style between discordant MA twins (Ulrich et al. 2000). Furthermore, menstrual migraine is related to MO but not to MA suggesting a greater hormonal background for MO than MA (Headache Subcommittee of the International Headache Society 2004).