Schizophrenia susceptibility loci on chromosomes 13q32 and 8p21 (original) (raw)

Nature Genetics volume 20, pages 70–73 (1998)Cite this article

Abstract

Schizophrenia is a common disorder characterized by psychotic symptoms; diagnostic criteria have been established1. Family, twin and adoption studies suggest that both genetic and environmental factors influence susceptibility (heritability is approximately 71%; ref. 2), however, little is known about the aetiology of schizophrenia. Clinical and family studies suggest aetiological heterogeneity3,6. Previously, we reported that regions on chromosomes 22, 3 and 8 may be associated with susceptibility to schizophrenia7,8, and collaborations provided some support for regions on chromosomes 8 and 22 (refs 9, 10, 11, 12, 13). We present here a genome-wide scan for schizophrenia susceptibility loci (SSL) using 452 microsatellite markers on 54 multiplex pedigrees. Non-parametric linkage (NPL) analysis provided significant evidence for an SSL on chromosome 13q32 (NPL score = 4.18; P = 0.00002), and suggestive evidence for another SSL on chromosome 8p21–22 (NPL = 3.64; P = 0.0001). Parametric linkage analysis provided additional support for these SSL. Linkage evidence at chromosome 8 is weaker than that at chromosome 13, so it is more probable that chromosome 8 may be a false positive linkage. Additional putative SSL were noted on chromosomes 14q13 (NPL = 2.57; P = 0.005), 7q11 (NPL = 2.50, P = 0.007) and 22q11 (NPL = 2.42, P = 0.009). Verification of suggestive SSL on chromosomes 13q and 8p was attempted in a follow-up sample of 51 multiplex pedigrees. This analysis confirmed the SSL in 13q14-q33 (NPL = 2.36, P = 0.007) and supported the SSL in 8p22-p21 (NPL = 1.95, P = 0.023).

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Acknowledgements

This work was supported by funding from Novartis Pharmaceuticals (1995-1998), grants from the National Institutes of Mental Health (NIMH; 1989-1995; R01 MH-45588 and 1 R01 35712), the National Institutes of Health (NIH) grant DRR-OPD-GCRC RR00722, the National Alliance for Research on Schizophrenia and Depression and gifts from private foundations and private donors. We wish to thank the patients and their families and the mental health professionals who referred patients and provided information.

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Author notes

  1. David E. Housman: Center For Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 , USA. J.-L.B., B.A.D. & S.K.N. contributed equally to this work.

Authors and Affiliations

  1. Division of Medical Genetics, University of Geneva Medical School and Cantonal Hospital, Geneva, 1211, Switzerland
    Jean-Louis Blouin, Corinne Gehrig, Uppala Radhakrishna & Stylianos E. Antonarakis
  2. Department of Genetics, University of Pennsylvania, Philadelphia, 19104, Pennsylvania, USA
    Beth A. Dombroski, Sarah E. Snyder, Katherine G. Balk & Haig H. Kazazian
  3. Department of Genetics and Center for Human Genetics, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, 44106, Ohio, USA
    Swapan K. Nath & Aravinda Chakravarti
  4. Department of Psychiatry and Behavioral Sciences, The Johns Hopkins School of Medicine, Baltimore, 21231, Maryland , USA
    Virginia K. Lasseter, Paula S. Wolyniec, Gerald Nestadt, Mary Thornquist, Gail Ullrich, John McGrath, Laura Kasch, Malgorzata Lamacz, Marion G. Thomas, Karin Neufeld, Karen L. Swartz, Barton Childs & Ann E. Pulver
  5. Seconda Universita di Napoli, Instituto di Psichiatria , Napoli, 80138, Italy
    Nicola DeMarchi
  6. University Mental Health Research Institute, Eginition Hospital, Athens, 115 28, Greece
    George N. Papadimitriou, Dimitris G. Dikeos & Costas N. Stefanis

Authors

  1. Jean-Louis Blouin
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  2. Beth A. Dombroski
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  3. Swapan K. Nath
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  4. Virginia K. Lasseter
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  5. Paula S. Wolyniec
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  6. Gerald Nestadt
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  7. Mary Thornquist
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  8. Gail Ullrich
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  9. John McGrath
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  10. Laura Kasch
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  11. Malgorzata Lamacz
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  12. Marion G. Thomas
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  13. Corinne Gehrig
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  14. Uppala Radhakrishna
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  15. Sarah E. Snyder
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  16. Katherine G. Balk
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  17. Karin Neufeld
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  18. Karen L. Swartz
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  19. Nicola DeMarchi
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  20. George N. Papadimitriou
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  21. Dimitris G. Dikeos
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  22. Costas N. Stefanis
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  23. Aravinda Chakravarti
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  24. Barton Childs
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  25. David E. Housman
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  26. Haig H. Kazazian
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  27. Stylianos E. Antonarakis
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  28. Ann E. Pulver
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Corresponding author

Correspondence toAnn E. Pulver.

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Blouin, JL., Dombroski, B., Nath, S. et al. Schizophrenia susceptibility loci on chromosomes 13q32 and 8p21.Nat Genet 20, 70–73 (1998). https://doi.org/10.1038/1734

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