title: Association of DISC1 gene with schizophrenia in families from two distinct French and Algerian populations.
abstract: OBJECTIVE
  The Disrupted-in-Schizophrenia-1 (DISC1) gene is a promising genetic risk factor for major mental illnesses, especially schizophrenia. Several variants encompassing the DISC1 gene have been associated with schizophrenia and specific clinical features. Negative results were nevertheless observed, stratification biases, heterogeneity of the analyzed samples and low statistical power being potentially involved.
  
  
  METHODS
  We analyzed four single nucleotide polymorphisms (SNPs), including three non-synonymous SNPs, of DISC1 in two independent samples of trios, from France and Algeria, using family-based association tests to elude statistical limits.
  
  
  RESULTS
  In 114 French schizophrenia trios, the C allele of non-synonymous rs6675281/Leu607Phe/C1872T was significantly over-transmitted [odds ratio (OR)=2.3, 95% confidence interval (CI)=1.1-4.4]. This same SNP was also more frequently transmitted in the 100 Algerian schizophrenia trios (OR=2.6, 95% CI=0.9-7.3). In the combined 214 trios, a significant over-transmission of the C allele of rs6675281 to the affected probands was observed (P=0.002), even after correction for multiple testing (P corrected=0.01 OR=2.4 and 95% CI=1.3-4.2). Assessing if a dimension of schizophrenia could be more specifically involved, we found that patients with the C allele had a significantly higher Scale for the Assessment of Negative Symptoms total score (P=0.0002).
  
  
  CONCLUSIONS
  The analysis adds convergent evidence in favor of a significant role of the DISC1 gene as a risk factor for schizophrenia, as present in two different samples, in family trios rather than with a case--control approach, and even when multiple tests are controlled for. We could further potentially attribute this effect to the negative dimension of schizophrenia.
authors.affiliation: INSERM, Centre de Psychiatrie et Neurosciences, Université Paris Descartes, Paris, France.
authors.forename: Aude-Marie
authors.initials: AM
authors.lastname: Lepagnol-Bestel
authors.forename: Caroline
authors.initials: C
authors.lastname: Dubertret
authors.forename: Dalila
authors.initials: D
authors.lastname: Benmessaoud
authors.forename: Michel
authors.initials: M
authors.lastname: Simonneau
authors.forename: Jean
authors.initials: J
authors.lastname: Adès
authors.forename: Farid
authors.initials: F
authors.lastname: Kacha
authors.forename: Nora
authors.initials: N
authors.lastname: Hamdani
authors.forename: Philip
authors.initials: P
authors.lastname: Gorwood
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ramoz
mesh_terms: D000462:Algeria; D003710:Demography; D005190:Family; D005260:Female; D005602:France; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics*; D055815:Young Adult
chemical_list: C412476:DISC1 protein, human; D009419:Nerve Tissue Proteins