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Test of Xq26.3–28 linkage in bipolar and unipolar affective disorder in families selected for absence of male to male transmission

Published online by Cambridge University Press:  02 January 2018

Ciaran Smyth
Affiliation:
Molecular Psychiatry Laboratory, University College London Medical School
Gursharan Kalsi
Affiliation:
Molecular Psychiatry Laboratory, University College London Medical School
Jon Brynjolfsson
Affiliation:
Department of Psychiatry, University of Iceland
Jane O'Neill
Affiliation:
Molecular Psychiatry Laboratory, UCL Medical School
David Curtis
Affiliation:
Academic Department of Psychiatry, St Bartholomew's and Royal London School of Medicine and Dentistry, Whitechapel, London E1 1BB
Larry Rifkin
Affiliation:
Molecular Psychiatry Laboratory, UCL Medical School
Eamon Moloney
Affiliation:
Molecular Psychiatry Laboratory, UCL Medical School
Patrice Murphy
Affiliation:
Molecular Psychiatry Laboratory, UCL Medical School
Hannes Petursson
Affiliation:
Department of Psychiatry, Borgarspitalinn, Reýkjavik 108, Iceland
Hugh Gurling*
Affiliation:
Molecular Psychiatry Laboratory, UCL Medical School
*
Professor H. Gurling, Molecular Psychiatry Laboratory, University College London Medical School, Windeyer Building, 46 Cleveland Street, London WIP 6DB. Fax: 0171 436 5046; e-mail: [email protected]

Abstract

Background

There have been several reports of linkage between genetic markers on the X chromosome at Xq26.3-28 and bipolar affective disorder in family samples obtained from distinct ethnic and geographical origins. As part of a genome search in a series of 23 UK and Icelandic families, specifically selected for their large size and power to resolve the issue of linkage heterogeneity, we have tested the hypothesis that there is a locus for a genetic subtype of bipolar affective disorder which is linked to this region.

Method

In families selected on the basis of absent male to male transmission for affective disorder, we performed two-point and FASTMAP multipoint linkage analyses with markers spanning the region between the genetic loci DXS102 and F8

Results

We found negative lod scores for several models of affection status in families selected under stringent and relaxed criteria for the absence of male to male transmission.

Conclusions

In the family sample we have obtained, our study provides no support for the presence of a locus increasing genetic susceptibility to bipolar affective disorder in this region of the X chromosome. It is likely that our finding reflects heterogeneity of linkage for bipolar and genetically related unipolar disorder that exists in specific ethnic populations. Alternatively the X-linked subtype of the disorder may have been present only in a few of our small families resulting in loss of power to detect the Xq26.3-28 linked subtype.

Type
Papers
Copyright
Copyright © 1997 The Royal College of Psychiatrists 

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References

Baron, M. (1977) Linkage between an X chromosome marker (deutan colour blindness) and affective illness. Archives of General Psychiatry, 24, 721727.CrossRefGoogle Scholar
Baron, M., Risch, N., Hamburger, R., et al (1987) Genetic linkage between X chromosome markers & bipolar affective disorder. Nature, 326, 289292.CrossRefGoogle Scholar
Baron, M., Freimer, N. F., Risch, N., et al (1993) Diminished support for linkage between manic depressive illness and X-chromosome markers in three Israeli pedigrees. Nature Genetics, 3, 4955.Google Scholar
Berrettini, W. H., Goldin, L. R., Gelernter, J., et al (1990) X-chromosome markers and manic–depressive illness. Rejection of linkage to Xq28 in nine bipolar pedigrees. Archives of General Psychiatry, 47, 366373.Google Scholar
Curtis, D. & Gurling, H. M. D. (1991) Using a dummy quantitative variable to deal with multiple affection categories in genetic linkage analysis. Annals of Human Genetics, 55. 321327.Google Scholar
Curtis, D., Brynjolfsson, J., Petursson, H., et al (1993) Segregation and linkage analysis in five manic depression pedigrees excludes the 5HTI1a receptor gene (HTRIA). Annals of Human Genetics, 54, 365367.Google Scholar
Curtis, D. & Gurling, H. M. D. (1993) A procedure for combining two-point lod scores into a summary multipoint map. Human Heredity, 43, 173185.CrossRefGoogle ScholarPubMed
Endicott, J. & Spitzer, R. (1978) A diagnostic interview: The schedule for affective disorders and schizophrenia. Archives of General Psychiatry, 35, 837862.Google Scholar
Gejman, P. V., Detra-Wadleigh, S., Martinez, M., et al (1990) Manic depressive illness not linked to Factor 9 region in an independent series of pedigrees. Genomics, 8, 648655.Google Scholar
Gershon, E. S., Targum, S. D., Matthyse, S., et al (1979) Colour blindness not closely linked to bipolar illness. Archives of General Psychiatry, 36, 1423.Google Scholar
Goetzl, U., Green, R., Whybrow, P., et al (1974) X linkage revisited, a further study of manic depression. Archives of General Psychiatry, 31, 665672.Google Scholar
Holmes, D., Sherrington, R. P., Hodgkinson, S., et al (1989) Linkage analysis in manic depression families identifies a non 11p/nonX type. American Journal of Human Genetics, 45, A195.Google Scholar
Lalouel, J. M., Rao, D. L., Morton, N. E., et al (1983) A unified model for complex segregation analysis. American Journal of Human Genetics, 35, 816826.Google Scholar
Lathrop, M., Lalouel, J., Julier, C., et al (1985) Strategies for multilocus linkage analysis in human. Proceedings of the National Academy of Science USA, 81, 34433446.Google Scholar
Lucotte, G., Landoulsi, A., Berriche, S., et al (1992) Manic depressive illness is linked to factor IX in a French pedigree. Annales Génétique, 35, 9395.Google Scholar
Mendlewicz, J., Fleiss, J. L. & Fieve, R. R. (1972) Evidence for X linkage in the transmission of manic depressive illness. Journal of the American Medical Association, 222, 16241627.CrossRefGoogle ScholarPubMed
Mendlewicz, J. & Fleiss, J. L. (1974) Linkage studies with X chromosome markers in bipolar (manic–depressive) and unipolar (depressive) illness. Biological Psychiatry, 9, 261264.Google Scholar
Mendlewicz, J., Linkowski, P., Guroff, J. J., et al (1979) Colour blindness linkage to bipolar manic depressive illness. Archives of General Psychiatry, 36, 14421447.Google Scholar
Mendlewicz, J., Linkowski, P., & Wilmotte, J. (1980) Linkage between glucose 6-phosphate dehydrogenase deficiency and manic depressive psychosis. British Journal of Psychiatry, 134, 337342.Google Scholar
Mendlewicz, J., Simon, P., Sevy, S., et al (1987) Polymorphic marker on X chromosome and manic depression. Lancet. 8544, 12301231.Google Scholar
Miller, S. A., Dykes, D. D. & Polesky, H. F. (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acid Research, 16, 1215.Google Scholar
Pekkarinen, P., Terwilliger, J., Bredbacka, P.-E., et al (1995) Evidence of a predisposing locus to bipolar disorder on Xq24–q27.1 in an extended Finnish Pedigree. Genetic Research. 5, 105115.Google Scholar
Reading, C. M. (1979) X linked dominant manic depressive illness: Linkage with Xg blood group, red green colour blindness and vitamin B12 deficiency. Orthomolecular Psychiatry, 8, 6877.Google Scholar
Reich, T., Clayton, P. J. & Winokur, G. (1969) Family history studies-V. The genetics of mania. American Journal of Psychiatry, 125, 13581369.CrossRefGoogle ScholarPubMed
Reich, T. & Baron, M. (1982) X linked and genetic heterogeneity in bipolar related major affective illness: reanalysis of linkage data. Annals of Human Genetics, 46, 153166.Google Scholar
Risch, N. (1989) Linkage detection tests under heterogeneity. Genetic Epidemiology, 6, 473480.Google Scholar
Schlessinger, D., Little, R. D., Freije, D., et al (1991) Yeast artificial chromosome based genome mapping: some lessons from Xq24–28. Genomics, 11, 783793.CrossRefGoogle Scholar
Spitzer, R. L., Endicott, J. & Robins, E. (1978) Research Diagnostic Criteria for a Selected Group of Functional Disorders (3rd edn). New York: New York State Psychiatric Institute.Google Scholar
Winokur, G. & Tanna, V. L. (1969) Possible role of X linked dominant factor in manic depressive disease. Diseases of the Nervous System, 30, 8993.Google Scholar
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