Skip to main content
PMC home page
The Journal of Headache and Pain logoLink to The Journal of Headache and Pain
. 2007 Jun 11;8(3):190–195. doi: 10.1007/s10194-007-0389-4

Genetics in primary headaches

Michael Bjørn Russell 1,2,3,4,✉
PMCID: PMC2780622  PMID: 17563838

Abstract

This tutorial describes different methods and results of genetic studies of primary headaches. A positive family history is imprecise, because it does not specify the number of affected, family size or relation to the proband. Nor does it include an interview of the possibly affected family members. Calculation of the familial aggregation after confirmation of the diagnosis by a physician is more precise. Compared to the general population, first-degree relatives of probands with migraine without aura, migraine with aura, chronic tension-type headache and cluster headache has a significantly increased risk of the proband’s disorder. These data are confirmed in twin studies. The primary headaches are caused by a combination of genetic and environmental factors. A major breakthrough was identification of 3 different genes all causing the rare autosomal dominant inherited familial hemiplegic migraine. The genes encode ion channels. So far no genes have been identified to cause the more common types of primary headaches.

Keywords: Migraine, cluster, headache, tension-type headache, genetics, primary headache

Full Text

The Full Text of this article is available as a PDF (53.9 KB).

References

  • 1.Headache Classification Subcommittee of the International Headache Society The International Classification of Headache Disorders. Cephalalgia. 2004;24([Suppl1]):9–160. doi: 10.1111/j.1468-2982.2003.00824.x. [DOI] [PubMed] [Google Scholar]
  • 2.Russell M.B. Genetic epidemiology of migraine and cluster headache. University of Copenhagen. Cephalalgia. 1997;17:683–701. doi: 10.1046/j.1468-2982.1997.1706683.x. [DOI] [PubMed] [Google Scholar]
  • 3.Russell M.B. Tension-type headache in 40-year-olds: a Danish population-based sample of 4000. J Headache Pain. 2005;6:441–447. doi: 10.1007/s10194-005-0253-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Rasmussen B.K., Jensen R., Schroll M., Olesen J. Epidemiology of headache in a general population — a prevalence study. J Clin Epidemiol. 1991;44:1147–1157. doi: 10.1016/0895-4356(91)90147-2. [DOI] [PubMed] [Google Scholar]
  • 5.Russell M.B., Fenger K., Olesen J. The family history of migraine. Direct versus indirect information. Cephalalgia. 1996;16:156–160. doi: 10.1046/j.1468-2982.1996.1603156.x. [DOI] [PubMed] [Google Scholar]
  • 6.Weiss K.M., Chakraborty R., Majumder P.P., Smouse P.E. Problems in the assessment of relative risk of affected individuals. J Chronic Dis. 1982;35:539–551. doi: 10.1016/0021-9681(82)90073-X. [DOI] [PubMed] [Google Scholar]
  • 7.Mochi M., Sangiorgi S., Cortelli P., et al. Testing models for genetic determination in migraine. Cephalalgia. 1993;13:389–394. doi: 10.1046/j.1468-2982.1993.1306389.x. [DOI] [PubMed] [Google Scholar]
  • 8.Russell M.B., Olesen J. Increased familial risk and evidence of genetic factor in migraine. Br Med J. 1995;311:541–544. doi: 10.1136/bmj.311.7004.541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Kalfakis N., Panas M., Vassilopoulos D., Malliara Loulakaki S. Migraine with aura: segregation analysis and heritability estimation. Headache. 1996;36:320–322. doi: 10.1046/j.1526-4610.1996.3605320.x. [DOI] [PubMed] [Google Scholar]
  • 10.Stewart W.F., Staffa J., Lipton R.B., Ottman R. Familial risk of migraine: a population based study. Ann Neurol. 1997;41:166–172. doi: 10.1002/ana.410410207. [DOI] [PubMed] [Google Scholar]
  • 11.Østergaard S., Russell M.B., Bendtsen L., Olesen J. Comparison of first degree relatives and spouses of people with chronic tension type headache. Br Med J. 1997;314:1092–1093. doi: 10.1136/bmj.314.7087.1092. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Russell M.B., Andersson P.G., Thomsen L.L. Familial occurrence of cluster headache. J Neurol Neurosurg Psychiatry. 1995;58:341–343. doi: 10.1136/jnnp.58.3.341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Kudrow L., Kudrow D.B. Inheritance of cluster headache and its possible link to migraine. Headache. 1994;34:400–407. doi: 10.1111/j.1526-4610.1994.hed3407400.x. [DOI] [PubMed] [Google Scholar]
  • 14.Leone M., Russell M.B., Rigamonti A., et al. Familial risk of cluster headache: a study of Italian families. Neurology. 2001;56:1233–1236. doi: 10.1212/wnl.56.9.1233. [DOI] [PubMed] [Google Scholar]
  • 15.Amrani M., Ducros A., Boulan P., et al. Familial cluster headache: a series of 186 index patients. Headache. 2002;42:974–977. doi: 10.1046/j.1526-4610.2002.02226.x. [DOI] [PubMed] [Google Scholar]
  • 16.Russell M.B. Epidemiology and genetics of cluster headache. Lancet Neurol. 2004;3:279–283. doi: 10.1016/S1474-4422(04)00735-5. [DOI] [PubMed] [Google Scholar]
  • 17.Khoury M.J., Beaty T.H., Liang K.-Y. Can familial aggregation of diseases be explained by familial aggregation of environmental risk factors? Am J Epidemiol. 1988;127:674–683. doi: 10.1093/oxfordjournals.aje.a114842. [DOI] [PubMed] [Google Scholar]
  • 18.Ulrich V., Gervil M., Kyvik K.O., et al. Evidence of a genetic factor in migraine with aura: a population-based Danish twin study. Ann Neurol. 1999;45:242–246. doi: 10.1002/1531-8249(199902)45:2<242::AID-ANA15>3.0.CO;2-1. [DOI] [PubMed] [Google Scholar]
  • 19.Gervil M., Ulrich V., Kyvik K.O., et al. Migraine without aura: A population based twin study. Ann Neurol. 1999;46:606–611. doi: 10.1002/1531-8249(199910)46:4<606::AID-ANA8>3.0.CO;2-O. [DOI] [PubMed] [Google Scholar]
  • 20.Motulsky A.G. Biased ascertainment and the natural history of diseases. N Engl J Med. 1978;298:1196–1197. doi: 10.1056/NEJM197805252982111. [DOI] [PubMed] [Google Scholar]
  • 21.Svensson D., Ekbom K., Pedersen N.L., et al. A note on cluster headache in a population-based twin registry. Cephalalgia. 2003;5:376–380. doi: 10.1046/j.1468-2982.2003.00521.x. [DOI] [PubMed] [Google Scholar]
  • 22.Russell M.B., Saltyte-Benth J., Levi N. Are infrequent episodic, frequent episodic and chronic tension-type headache inherited? A population-based study of 11 199 twin pairs. J Headache Pain. 2006;7:119–126. doi: 10.1007/s10194-006-0299-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Lalouel J.M., Morton N.E. Complex segregation analysis with pointers. Hum Hered. 1981;31:312–321. doi: 10.1159/000153231. [DOI] [PubMed] [Google Scholar]
  • 24.Russell M.B., Iselius L., Olesen J. Investigation of inheritance of migraine by complex segregation analysis. Hum Genet. 1995;96:726–730. doi: 10.1007/BF00210307. [DOI] [PubMed] [Google Scholar]
  • 25.Russell M.B., Iselius L., Østergaard S., Olesen J. A complex segregation analysis of chronic tension-type headache. Hum Genet. 1998;102:138–140. doi: 10.1007/s004390050666. [DOI] [PubMed] [Google Scholar]
  • 26.Russell M.B., Andersson P.G., Thomsen L.L., Iselius L. Cluster headache is an autosomal dominant inherited disorder in some families. A complex segregation analysis. J Med Genet. 1995;32:954–956. doi: 10.1136/jmg.32.12.954. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Simone R., Fiorillo C., Bonuso S., Castaldo G. A cluster headache family with possible autosomal recessive inheritance. Neurology. 2003;61:578–579. doi: 10.1212/01.wnl.0000078698.05379.ff. [DOI] [PubMed] [Google Scholar]
  • 28.Ducros A., Tournier-Lasserve E., Bousser M.G. The genetics of migraine. Lancet Neurol. 2002;1:285–293. doi: 10.1016/S1474-4422(02)00134-5. [DOI] [PubMed] [Google Scholar]
  • 29.Thomsen L.L., Ostergaard E., Romer S.F., et al. Evidence for a separate type of migraine with aura: sporadic hemiplegic migraine. Neurology. 2003;60:595–601. doi: 10.1212/01.wnl.0000046524.25369.7d. [DOI] [PubMed] [Google Scholar]
  • 30.Ophoff R.A., Terwindt G.M., Vergouwe M.N., et al. Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4. Cell. 1996;87:543–552. doi: 10.1016/S0092-8674(00)81373-2. [DOI] [PubMed] [Google Scholar]
  • 31.Fusco M., Marconi R., Silvestri L., et al. Haploinsufficiency of ATP1A2 encoding the Na+/K+ pump alpha2 subunit associated with familial hemiplegic migraine type 2. Nat Genet. 2003;33:192–196. doi: 10.1038/ng1081. [DOI] [PubMed] [Google Scholar]
  • 32.Dichgans M., Freilinger T., Eckstein G., et al. Mutation in the neuronal voltage-gated sodium channel SCN1A in familial hemiplegic migraine. Lancet. 2005;366:371–377. doi: 10.1016/S0140-6736(05)66786-4. [DOI] [PubMed] [Google Scholar]
  • 33.Russell M.B., Olesen J. A nosographic analysis of the migraine aura in the general population. Brain. 1996;119:355–361. doi: 10.1093/brain/119.2.355. [DOI] [PubMed] [Google Scholar]
  • 34.Joutel A., Bousser M.G., Biousse V. A gene for familial hemiplegic migraine maps to chromosome 19. Nat Genet. 1993;5:40–45. doi: 10.1038/ng0993-40. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Headache and Pain are provided here courtesy of BMC

RESOURCES