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Investigation by Linkage Analysis of the XY Pseudoautosomal Region in the Genetic Susceptibility to Schizophrenia

  • Gursharan Kalsi (a1), David Curtis (a2), Jon Brynjolfsson (a3), Robert Butler (a1), Tonmoy Sharma (a1), Patrice Murphy (a1), Tim Read (a1), Hannes Petursson (a3) and Hugh M. D. Gurling (a1)...

Abstract

Background

A susceptibility locus for schizophrenia in the pseudoautosomal region has been proposed on the basis of a possible excess of sex chromosome aneuploidies among patients with schizophrenia and an increased sex concordance in affected sib pairs. Several studies investigating this hypothesis have produced conflicting evidence.

Method

In a series of Icelandic and British families, we used lod score and sib pair linkage analyses with markers for the MIC2 and DXYS14 loci on the pseudoautosomal XY region.

Results

Lod and sib pair linkage analysis with these markers produced strongly negative scores. Heterogeneity testing also produced negative results.

Conclusion

We conclude that the present study provides no support for the involvement of either the pseudoautosomal region or the nearby region of the sex chromosomes in the aetiology of schizophrenia.

Copyright

Corresponding author

Dr Gurling, Molecular Psychiatry Laboratory, Department of Psychiatry, University College London Medical School, Riding House Street, London W1P 7PN

References

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Asherson, P., Parfitt, M., Sargeant, M., et al (1992) No evidence for a pseudoautosomal locus for schizophrenia. Linkage analysis of multiply affected families. British Journal of Psychiatry, 161, 6368.
Barr, C. L., Kennedy, J. L., Pakstis, A. J., et al (1994) Linkage study of susceptibility locus for schizophrenia in the pseudoautosomal region. Schizophrenia Bulletin, 20, 277286.
Collinge, J. S., DeLisi, L. E. & Boccio, A. (1991) Evidence for a pseudoautosomal locus for schizophrenia using the method of affected sib pairs. British Journal of Psychiatry, 158, 624629.
Crow, T. J. (1988) Sex chromosomes and psychosis. The case for a pseudoautosomal locus. British Journal of Psychiatry, 153, 675683.
Crow, T. J., DeLisi, L. E. & Johnstone, E. C. (1989) Concordance by sex in sibling pairs with schizophrenia is paternally inherited. Evidence for a pseudoautosomal locus. British Journal of Psychiatry, 155, 9297.
Crow, T. J., DeLisi, L. E. Lofthouse, R., et al (1994) An examination of linkage of schizophrenia and schizoaffective disorder to the pseudoautosomal region (Xp22.3). British Journal of Psychiatry, 164, 159164.
Curtis, D., Kalsi, G. & Gurling, H. M. D. (1994) Pseudoautosomal linkage in schizophrenia (letter). British Journal of Psychiatry, 165, 117118.
D'Amato, T., Campion, D., Gorwood, P., et al (1992) Evidence for a pseudoautosomal locus for schizophrenia II: Replication of a non-random segregation of alleles at the DXYS14 locus. British Journal of Psychiatry, 161, 5962.
Gorwood, P., Leboyer, M., D'Amato, T., et al (1992) Evidence for a pseudoautosomal locus for schizophrenia I: A replication study using phenotype analysis. British Journal of Psychiatry, 161, 5558.
Penrose, L. S. (1942) Auxiliary genes for determining sex as contributory causes of mental illness. Journal of Mental Science, 88, 308316.
Wang, Z. W., Black, D., Andreasen, N., et al (1993) Pseudoautosomal locus for schizophrenia excluded in 12 pedigrees. Archives of General Psychiatry, 50, 199204.

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Investigation by Linkage Analysis of the XY Pseudoautosomal Region in the Genetic Susceptibility to Schizophrenia

  • Gursharan Kalsi (a1), David Curtis (a2), Jon Brynjolfsson (a3), Robert Butler (a1), Tonmoy Sharma (a1), Patrice Murphy (a1), Tim Read (a1), Hannes Petursson (a3) and Hugh M. D. Gurling (a1)...
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