title: Analysis of CpG SNPs in 34 genes: association test with suicide attempt in schizophrenia.
abstract: BACKGROUND
  Suicide is the act of intentionally causing one's own death. The lifetime suicide risk in schizophrenia is 4.9% and 20% to 50% of patients with SCZ will attempt suicide during their life. The other risk factors for suicidal behavior in schizophrenia include prior history of suicide attempts, active psychosis, depression and substance abuse. To date, there are no robust genetic or epigenetic predictors of suicide or suicide attempt in this specific population.
  
  
  METHODS
  We collected detailed clinical information and DNA samples from 241 schizophrenia patients and performed the genetic analyses in suicide attempters and non-attempters, among these patients. Using the structured research interview, we determined the presence of suicide attempt lifetime and then we tested 384 DNA variants in candidate genes supposed to be involved in the neurobiology of schizophrenia. We applied a novel mapping analysis using a specific bioinformatic tool that analyzed only the polymorphic CpG sites in our SNP panel. This analysis looked at the presence or absence of methylation sites affected by the SNP allele. The SNPs in the candidate genes were studied under a different perspective considering their direct contribution to the availability of methylation sites within the gene of interest. The level of potential methylation was compared using a linear model in attempters and non-attempters.
  
  
  RESULTS
  Among the 384 SNPs selected from the Illumina Bead Chip only the rs2661319 in the RGS4 gene was significantly associated with suicide attempt (p = 0.002). There were 119 CpG SNPs in the aforementioned panel. The gene-wise potential methylation level of RGS4 was 55% in the attempters and 65% in the non-attempters with a p-value of 0.005. The total level of potential metylation in the overall panel (119 SNPs combined) was not associated with suicide attempt. However, when considering the potential methylation at chromosome 1, we found that suicide attempt (p = 0.036) was associated with lower methylation.
  
  
  CONCLUSIONS
  The overall results showed no strong association between CpG SNPs and suicide attempt but the information regarding the CpG SNP potential methylation could be used as covariate in future methylation analysis.
authors.affiliation: CAMH, Department of Psychiatry, University of Toronto, Canada.
authors.forename: Ali
authors.initials: A
authors.lastname: Bani-Fatemi
authors.forename: Vanessa F
authors.initials: VF
authors.lastname: Gonçalves
authors.forename: Clement
authors.initials: C
authors.lastname: Zai
authors.forename: Renan
authors.initials: R
authors.lastname: de Souza
authors.forename: Bernard
authors.initials: B
authors.lastname: Le Foll
authors.forename: James L
authors.initials: JL
authors.lastname: Kennedy
authors.forename: Albert H
authors.initials: AH
authors.lastname: Wong
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Luca
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019175:DNA Methylation / Q000235:genetics; D015226:Dinucleoside Phosphates / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D025341:Principal Component Analysis; D012559:Schizophrenia / Q000235:genetics*; D012565:Schizophrenic Psychology; D013406:Suicide, Attempted / Q000523:psychology*; D055815:Young Adult
chemical_list: D015226:Dinucleoside Phosphates; C015772:CpG dinucleotide