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NEUROLOGY 2006;66:1888-1893
© 2006 American Academy of Neurology

A genome-wide scan and HCRTR2 candidate gene analysis in a European cluster headache cohort

L. Baumber, BSc, C. Sjöstrand, MD, M. Leone, MD, H. Harty, BSc, G. Bussone, MD, J. Hillert, MD, PhD, R. C. Trembath, BSc, FRCP and M. B. Russell, MD, PhD, DMSci

From the Division of Medical Genetics (L.B., H.H., R.C.T.), University of Leicester, UK; Department of Neurology (C.S., J.H.), Karolinska Institute, Karolinska University Hospital, Huddinge, Sweden; Carlo Besta National Neurological Institute (M.L., G.B.), Milan, Italy; Head and Neck Research Group, Akershus University Hospital, and Faculty Division, Akershus University Hospital (M.B.R.), University of Oslo, Norway; and Division of Medical & Molecular Genetics (L.B., R.C.T.), King’s College London (Guy’s Campus), Guy’s Hospital, London, UK.

Address correspondence and reprint requests to Dr. Richard C. Trembath, Professor of Medical Genetics, Division of Medical & Molecular Genetics, King’s College London Medical School (Guy’s Campus), Floor 7, Guy’s Tower, Guy’s Hospital, London SE1 9RT, UK; e-mail: richard.trembath{at}genetics.kcl.ac.uk

Objective: To investigate the molecular genetic basis of cluster headache (CH), using a genome-wide scan and candidate gene strategy.

Methods: Northern European CH families and a case-control cohort of Danish, Swedish, and British origin (total n = 259 sporadic CH patients), including 267 control subjects matched for ancestry, participated in the study. A genome-wide genetic screen using approximately 400 microsatellite markers was performed for five informative Danish CH families. Additional markers were typed for those loci generating statistical evidence suggestive of linkage, together with genotypes for 111 individuals from further Danish and Italian kindreds. Sporadic CH patients and controls were investigated by association analysis for variation in the candidate gene, HCRTR2. Finally, complete HCRTR2 sequencing was undertaken for eight independent probands.

Results: Potential linkage was identified at four possible disease loci in Danish kindreds, yet no single chromosome location generated a lod or NPL score of recognized significance. No deleterious sequence variants of the HCRTR2 gene were detected by comparison to wild-type sequence. Association of the HCRTR2 gene was not replicated in this large dataset, even when the data were stratified into distinct populations.

Conclusions: Cluster headache is a complex genetic disorder, with possible phenotypic and genetic heterogeneity compounding attempts at gene identification.

See also page 1917

Disclosure: The authors report no conflicts of interest.

Received July 26, 2005. Accepted in final form March 10, 2006.


Related Article

Cluster headache is associated with the G1246A polymorphism in the hypocretin receptor 2 gene
M. Schürks, T. Kurth, I. Geissler, G. Tessmann, H. -C. Diener, and D. Rosskopf
Neurology 2006 66: 1917-1919. [Abstract] [Full Text] [PDF]





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