Table
1 shows the familial aggregation in family studies of migraine without aura, migraine with aura, chronic tension-type headache and cluster headache. All surveys except the one by Stewart et al. found that first-degree relatives of probands had a significantly increased risk of the proband’s disorder as compared to the general population [
7‐
15]. The study by Stewart et al. is biased because family members were interviewed only about their most severe type of headache by lay interviewers [
10]. For an unerring diagnosis, interviews by physicians are preferred. Clinic populations are subject to selection bias. Thus, the study by Russell and Olesen conducted by one physician who was blinded to the diagnosis of the probands is probably the most precise genetic epidemiological survey on migraine [
8]. Tension-type headache is far more prevalent than migraine and for that reason possible genetic mechanisms cannot be elucidated with a genetic epidemiological survey [
3,
4]. The International Classification of Headache Disorders classifies tension-type headache as infrequent episodic, frequent episodic and chronic tension-type headache [
1]. The frequency cutoff point is not based on scientific evidence, but is set arbitrarily. However, Østergaard et al. conducted a genetic epidemiological survey of chronic tension-type headache, as the prevalence is about 3% in the general population; for details see Table
1 [
11]. The different results of genetic epidemiological surveys on cluster headache can at least partly be explained by methodological differences [
12‐
15]. The survey by El Amrani et al. is the most accurate, because all first-degree relatives were directly interviewed by a physician [
15]. Russell et al. and Leone et al. probably underestimated the risk of cluster headache, as only those possibly affected were interviewed [
12,
14]. The survey by Kudrow and Kudrow either under- or overestimated the risk of cluster headache, depending on the balance between underestimation and misclassification by the probands [
13]. A diagnosis of cluster headache was confirmed in only 57%, while the remaining 43% had migraine in the cluster headache survey by Russell et al. [
12].
Table 1
Age and gender standardised risk of migraine without aura (MO), migraine with aura (MA), cluster headache (CH) and chronic tension-type headache (CTTH). The population relative risk is calculated by available data from the original articles by the author. The revised population relative risks on CH were calculated assuming the prevalence of cluster headache is 200 per 100.000 inhabitants [
16]. CI denotes confidence intervals
Migraine without aura | | | | | |
| Clinic | MO | 64 | 17.7 | 3.6 (1.1–6.1) |
| General | MO | 102 | 54.8 | 1.9 (1.6–2.2) |
| | MA | 42 | 29.2 | 1.4 (1.0–1.9) |
| General | MO | 30 | 21.0 | 1.4 (0.8–2.5) |
| | MA | 10 | 4.2 | 2.4(0.9–4) |
Migraine with aura | | | | | |
| Clinic | MA | 13 | 1.9 | 7.0 (3.2–10.8) |
| General | MA | 111 | 29.3 | 3.8 (3.2–4.4) |
| | MO | 56 | 54.9 | 1.0 (0.8–1.3) |
| Clinic | MA | 58 | 4.9 | 11.9 (7.0–16.7) |
| General | MA | 3 | 2.4 | 1.2 (0.3–5.5) |
| | MO | 17 | 12.1 | 1.4 (0.7–2.8) |
Chronic tension-type headache | | | | | |
| Clinic | CTTH | 71 | 22.6 | 3.1 (2.5–3.9) |
Cluster headache | | | | | |
| Clinic | CH | 26 | 5.40 | 4.7 (3.1–6.9) |
| | CH* | 10 | 13.20 | 0.8 (0.4–1.4) |
| Clinic | CH | 41 | 2.70 | 15.2 (11.1–21.1) |
| Clinic | CH | 39 | 2.97 | 13.1 (9.0–17.3) |
| | CH* | 18 | 6.69 | 2.7 (1.5–3.9) |
| Clinic | CH | 22 | 1.25 | 17.6 (10.2–24.9) |
An increased familial risk can be caused by genetic as well as environmental factors. The risk among spouses can be used to evaluate this relation, because probands and spouses in part share a common environment, but differ in genetic constitution. Spouses to probands with migraine without aura had a slightly increased risk of migraine without aura, while spouses to probands with migraine with aura had no increased risk of migraine with aura [
8]. Spouses to probands with chronic tension-type headache had no increased risk of chronic tension-type headache [
11]. Thus, the epidemiological surveys of migraine without aura, migraine with aura and chronic tension-type headache suggest the importance of genetic factors. The increased familial risk of cluster headache strongly suggests a genetic cause. Theoretically, a shared environment can produce relative risks of the magnitude observed for cluster headache only under extreme conditions [
17].