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Genome wide significant linkage in schizophrenia conditioning on occurrence of depressive episodes


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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