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Suggestive linkage of schizophrenia to 5p13 in Costa Rica

Molecular Psychiatry volume 10, pages 651–656 (2005)Cite this article

Abstract

Schizophrenia afflicts roughly 1% of all people worldwide. Remarkably, despite differing cultures and environments, the expression of illness is essentially the same. Family, twin, and adoption studies identify schizophrenia as a genetically influenced disease. Linkage studies suggest many positive regions of interest, but as a complex genetic disorder most of the pathogenic loci have not yet been found. Isolated populations are commonly used to study rare Mendelian inherited diseases due to the more homogenous genetic background of the subjects and are thought to be useful for detecting linkage in complex genetic disorders such as schizophrenia. This study aims to define areas of the genome that exhibit co-inheritance with schizophrenia in one large, Mendelian-like family from the central valley of Costa Rica. The whole genome scan analysis of this pedigree, which included 11 cases of schizophrenia and schizoaffective disorder, identified a number of markers on chromosome 5p that appear to co-segregate with the disease with a maximum lod score of 2.70 at marker D5S426. Current studies include investigating additional Costa Rican pedigrees to replicate these findings and identify additional loci linked to the disease.

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References

  1. Rice DP, Miller LS . Health economics and cost implications of anxiety and other mental disorders in the United States. Br J Psychiatry 1998; 173(Suppl 34): 4–9.

    Article  Google Scholar 

  2. Wyatt RJ, Henter I, Leary MC, Taylor E . An economic evaluation of schizophrenia—1991. Soc Psychiatry Psychiatr Epidemiol 1995; 30: 196–205.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Maier W, Rietschel M, Lichtermann D, Wildenauer DB . Family and genetic studies on the relationship of schizophrenia to affective disorders. Eur Arch Psychiatry Clin Neurosci 1999; 249(Suppl 4): 57–61.

    Article  Google Scholar 

  4. McGue M, Gottesman II . The genetic epidemiology of schizophrenia and the design of linkage studies. Eur Arch Psychiatry Clin Neurosci 1991; 240: 174–181.

    Article  CAS  Google Scholar 

  5. Kringlen E . Twin studies in schizophrenia with special emphasis on concordance figures. Am J Med Genet 2000; 97: 4–11.

    Article  CAS  Google Scholar 

  6. Gottesman II, Erlenmeyer-Kimling L . Family and twin strategies as a head start in defining prodromes and endophenotypes for hypothetical early-interventions in schizophrenia. Schizophr Res 2001; 51: 93–102.

    Article  CAS  Google Scholar 

  7. Shifman S, Darvasi A . The value of isolated populations. Nat Genet 2001; 28: 309–310.

    Article  CAS  Google Scholar 

  8. Reich DA, Cargill M, Bolk S, Ireland J, Sabeti PC, Richter DJ et al. Linkage disequilibrium in the human genome. Nature 2001; 411: 199–204.

    Article  CAS  Google Scholar 

  9. Mathews CA, Reus VI, Bejarano J, Escamilla MA, Fournier E, Herrera LD et al. Genetic studies of neuropsychiatric disorders in Costa Rica: a model for the use of isolated populations. Psychiatr Genet 2004; 14: 13–23.

    Article  Google Scholar 

  10. Carlos M . Historia de Costa Rica. Editorial Eidos: San Jose, Costa Rica, 1997, pp 407–417.

    Google Scholar 

  11. DeLisi LE, Mesen A, Rodriguez C, Bertheau A, LaPrade B, Llach M et al. Genome-wide scan for linkage to schizophrenia in a Spanish-origin cohort from Costa Rica. Am J Med Genet 2002; 114: 497–508.

    Article  Google Scholar 

  12. Morera B, Barrantes R, Marin-Rojas R . Gene admixture in the Costa Rican population. Ann Hum Genet 2003; 67(Part 1): 71–80.

    Article  CAS  Google Scholar 

  13. Fonseca E . Costa Rica colonial: La tierra y el hombre. EDUCA: San Jose, Costa Rica, 1983, pp 109–111.

    Google Scholar 

  14. Service SK, Ophoff RA, Freimer NB . The genome-wide distribution of background linkage disequilibrium in a population isolate. Hum Mol Genet 2001; 10: 545–551.

    Article  CAS  Google Scholar 

  15. Kurtz CL, Karolyi L, Seyberth HW, Koch MC, Vargas R, Feldmann D et al. A common NKCC2 mutation in Costa Rican Bartter's syndrome patients: evidence for a founder effect. J Am Soc Nephrol 1997; 8: 1706–1711.

    CAS  PubMed  Google Scholar 

  16. Leon PE, Raventos H, Lynch E, Morrow J, King MC . The gene for an inherited form of deafness maps to chromosome 5q31. Proc Natl Acad Sci USA 1992; 89: 5181–5184.

    Article  CAS  Google Scholar 

  17. Uhrhammer N, Lange E, Porras O, Naeim A, Chen X, Sheikavandi S et al. Sublocalization of an ataxia-telangiectasia gene distal to D11S384 by ancestral haplotyping in Costa Rican families. Am J Hum Genet 1995; 57: 103–111.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Gurling HM, Kalsi G, Brynjolfson J, Sigmundsson T, Sherrington R, Mankoo BS et al. Genomewide genetic linkage analysis confirms the presence of susceptibility loci for schizophrenia, on chromosomes 1q32.2, 5q33.2, and 8p21–22 and provides support for linkage to schizophrenia, on chromosomes 11q23.3-24 and 20q12.1–11.23. Am J Hum Genet 2001; 68: 661–673.

    Article  CAS  Google Scholar 

  19. Garver DL, Barnes R, Holcomb J, Filbey F, Wilson R, Bowcock A . Genome-wide scan and schizophrenia in African Americans. Am J Med Genet 1998; 81: 454–455.

    Google Scholar 

  20. Silverman JM, Greenberg DA, Altstiel LD, Siever LJ, Mohs RC, Smith CJ et al. Evidence of a locus for schizophrenia and related disorders on the short arm of chromosome 5 in a large pedigree. Am J Med Genet 1996; 67: 162–171.

    Article  CAS  Google Scholar 

  21. Bell GI, Karam JH, Rutter WJ . Polymorphic DNA region adjacent to the 5′ end of the human insulin gene. Proc Natl Acad Sci USA 1981; 78: 5759–5763.

    Article  CAS  Google Scholar 

  22. Chanda VA (Ed). Curr Protocols Mol Biol 1994; 2(Suppl 8): Appendix 3.

  23. Wroblewski JM, Copple A, Batson LP, Landers CD, Yanelli JR . Cell surface phenotyping and cytokine production of Epstein–Barr Virus (EBV)-transformed lymphoblastoid cell lines (LCLs). J Immunol Methods 2002; 264: 19–28.

    Article  CAS  Google Scholar 

  24. O’Connell JR, Weeks DE . Pedcheck: A program for identifying genotype incompatibilities in linkage analysis. Am J Hum Genet 1998; 63: 259–266.

    Article  Google Scholar 

  25. Byerley W, Devlin B, Bacanu SA, Roeder K, Reimherr F, Wender P et al. Genome-wide multipoint linkage analyses of multiplex schizophrenia pedigrees from the oceanic nation of Palau. Mol Psychiatry 2002; 7: 689–694.

    Article  Google Scholar 

  26. Straub RE, McLean CJ, O’Neill FA, Walsh D, Kendler KS . Support for a possible schizophrenia vulnerability locus in region 5q22–31 in Irish families. Mol Psychiatry 1997; 2: 148–155.

    Article  CAS  Google Scholar 

  27. DeLisi LE, Mesen A, Rodriguez C, Bertheau A, LaPrade B, Llach M et al. Clinical characteristics of schizophrenia in multiply affected Spanish origin families from Costa Rica. Psychiatr Gen 2001; 11: 145–152.

    Article  CAS  Google Scholar 

  28. Shaw SH, Kelly M, Smith AB, Shields G, Hopkins PJ, Loftus J et al. A genome-wide search for schizophrenia susceptibility genes. Am J Med Genet 1998; 81: 364–376.

    Article  CAS  Google Scholar 

  29. Sherrington R, Mankoo B, Dixon M, Curtis D, Kalsi G, Malmer G . Microsatellite polymorphisms for chromosome 5 bands q11.2–q13.3. Hum Hered 1993; 43: 197–202.

    Article  CAS  Google Scholar 

  30. Garver DL, Holcomb J, Mapau FM, Wilson R, Barnes B . Schizophrenia spectrum disorders: an autosomal-wide scan in multiplex pedigrees. Schizophr Res 2001; 52: 145–160.

    Article  CAS  Google Scholar 

  31. Escamilla MA, McInnes LA, Spesny M, Reus VI, Service SK, Shimayoshi N et al. Assessing the feasibility of linkage disequilibrium methods for mapping complex traits: an initial screen for bipolar disorder loci on chromosome 18. Am J Hum Genet 1999; 64: 1670–1678.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the Pritzker Neuropsychiatric Disorders Research Consortium, which is supported by the Pritzker Family Philanthropic Fund. A shared intellectual property agreement exists between the Pritzker Family Philanthropic Fund and all the universities involved, in order to encourage the development of appropriate findings for research and clinical applications. The academic and philanthropic entities involved in this Consortium are jointly filing patent applications related to the present findings. A special thanks to Lynn E DeLisi for developing this cohort of families in Costa Rica, supervising the clinical ascertainment, and performing final best estimate diagnoses. This study could not have been done without the genealogical tracing of individual families by Juan Rafael Sanabria, funded by NARSAD Junior Investigator Award (AM).

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Authors and Affiliations

  1. Department of Biological Chemistry, University of California, Irvine, Irvine, California, USA

    K Cooper-Casey & W Byerley

  2. Asociación Centro de Estudios Neuropsiquiátricos de Costa Rica (ACENP de Costa Rica), San José, Costa Rica

    A Mésen-Fainardi, M Llach, B Laprade & C Rodriguez

  3. Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA, USA

    B Galke-Rollins & W Byerley

  4. Hospital Nacional Psiquiátrico, Pavas, Costa Rica

    S Riondet & A Bertheau

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  1. K Cooper-Casey
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  2. A Mésen-Fainardi
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  3. B Galke-Rollins
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  4. M Llach
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  6. C Rodriguez
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  7. S Riondet
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  8. A Bertheau
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  9. W Byerley
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Correspondence to K Cooper-Casey.

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Cooper-Casey, K., Mésen-Fainardi, A., Galke-Rollins, B. et al. Suggestive linkage of schizophrenia to 5p13 in Costa Rica. Mol Psychiatry 10, 651–656 (2005). https://doi.org/10.1038/sj.mp.4001640

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