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Genome wide significant linkage in schizophrenia conditioning on occurrence of depressive episodes
  1. M L Hamshere1,2,
  2. N M Williams1,
  3. N Norton1,
  4. H Williams1,
  5. A G Cardno1,
  6. S Zammit1,
  7. L A Jones1,
  8. K C Murphy1,
  9. R D Sanders1,
  10. G McCarthy1,
  11. M Y Gray1,
  12. G Jones1,
  13. P Holmans2,
  14. M C O’Donovan1,
  15. M J Owen1,
  16. N Craddock1
  1. 1Department of Psychological Medicine, Wales School of Medicine, Cardiff University, Cardiff, UK
  2. 2Biostatistics and Bioinformatics Unit, Wales School of Medicine, Cardiff University, Cardiff, UK
  1. Correspondence to:
 Dr N Craddock
 Department of Psychological Medicine, School of Medicine, Cardiff University, Henry Wellcome Building, Heath Park, Cardiff, CF14 4XN, UK; craddockn{at}


Background: Schizophrenia shows substantial clinical heterogeneity. One common important clinical variable in presentation is the occurrence of episodes of major depression.

Methods: We undertook analyses in an attempt to detect loci that influence susceptibility to, or modify the clinical expression of, schizophrenia according to the occurrence of episodes of major depression. We used a logistic regression framework in which lifetime presence/absence of major depression was entered as a covariate in the linkage analysis of our UK schizophrenia affected sibling pair series (168 affected sibling pairs typed for a 10 cM map of microsatellite markers).

Results: Inclusion of presence/absence of depression as a covariate detected a genome wide significant linkage signal on chromosome 4q28.3 at 130.7 cM (LOD = 4.59; p = 0.038; increase in maximum LOD over univariate analysis (ILOD) = 3.62). Inclusion of the depression covariate also showed suggestive evidence of linkage on 20q11.21 (LOD = 4.10; expected to occur by chance 0.093 times per genome scan, ILOD = 2.83).

Conclusions: Our findings identify loci that may harbour genes that play a role in susceptibility to, or modify the risk of, episodes of major depression in people with schizophrenia.

  • ASPs, affected sibling pairs
  • DSM-IV, Diagnostic and statistical manual of mental disorders, 4th ed
  • IBD, identity by descent
  • ILOD, increase in logarithm of the odds ratio
  • OPCRIT, Operational Criteria Checklist
  • schizophrenia
  • depression
  • linkage
  • covariate
  • chromosome 4q

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  • Published Online First 14 October 2005

  • Competing interests: Professors Craddock and Owen are consultants to, and have received research grants from, GlaxoSmithkline. Professors Craddock, O’Donovan and Owen have received expenses and honoraria for lectures from several companies including GSK, AstraZeneca and Lilley. None of the authors has any competing financial interests in relation to any of the material within this manuscript.