Suicide appears to cluster in families, suggesting that genetic factors may play a role in this behavior. We studied 176 twin pairs in which one or both twins had committed suicide. Seven of the 62 monozygotic twin pairs were concordant for suicide compared with two of the 114 dizygotic twin pairs (11.3% vs 1.8%). The presence of psychiatric disorder in the twins and their families was examined in a subsample of 11 twin pairs, two of whom were concordant for suicide. Eleven of these 13 twin suicide victims had been treated for psychiatric disorder, as had eight of their nine surviving cotwins. In addition, twins in 10 pairs had other first- or second-degree relatives who had been treated for psychiatric disorder. Thus, these twin data suggest that genetic factors related to suicide may largely represent a genetic predisposition for the psychiatric disorders associated with suicide. However, they leave open the question of whether there may be an independent genetic component for suicide.
"A large number of studies in twins has also been reported. The pooled data from seven twin studies report concordance rates for suicide or suicide attempt of 23.5% in monozygotic twin pairs and 0.13% in dizygotic twins [12-14]. Furthermore, the classic adoption studies demonstrate higher suicide rates in the biological parents than in adoptive parents of adoptees who died by suicide [13,15]. "
[Show abstract][Hide abstract] ABSTRACT: The polymorphism COMTval158met has been associated with suicidal behavior in case-control and meta-analysis studies, but results and conclusions remain controversial. The objective of this study was to examine the association between COMT val158met with suicidal behavior in a case-control study and to assess the combined evidence -this case-control study and available data from other related studies- we carried out a meta-analysis.
We conducted a case-control study with 105 patients with suicide attempts and 236 controls. Subsequently, we performed a meta-analysis of published genetic association studies by searching through Medline, PubMed and Web of Science databases.
No significant differences were found in the distribution of alleles (χ2 = 0.33, 1 df, p = 0.56) or genotypes (χ2 = 2.36, 2 df, p = 0.26). The meta-analysis comprising 12 association studies (including the present one) showed that the risk COMTmet allele of COMTval158/met is not associated with suicidal behavior (OR: 1.09, 95% CI: 0.97-1.23), even in the absence of heterogeneity (OR: 1.09, 95% CI: 0.97-1.23).
Our results showed no association between COMTval158/met and suicidal behavior. However, more studies are necessary to determine conclusively an association between COMT and suicidal behavior.
"Analyses from pooled twin studies of completed suicide showed a higher concordance in monozygotic than dizygotic twins (11% v. 2%), with an estimated heritability of completed suicide of approximately 43% (95% CI 27–60%), with no contribution from shared family environment –. Such studies of the familiality of completed suicide are limited by the small numbers, but indicate the existence of genes contributing to suicidal behaviour. "
[Show abstract][Hide abstract] ABSTRACT: Suicidal behaviour can be conceptualised as a continuum from suicidal ideation, to suicidal attempts to completed suicide. In this study we identify genes contributing to suicidal behaviour in the depression study RADIANT.
A quantitative suicidality score was composed of two items from the SCAN interview. In addition, the 251 depression cases with a history of serious suicide attempts were classified to form a discrete trait. The quantitative trait was correlated with younger onset of depression and number of episodes of depression, but not with gender. A genome-wide association study of 2,023 depression cases was performed to identify genes that may contribute to suicidal behaviour. Two Munich depression studies were used as replication cohorts to test the most strongly associated SNPs. No SNP was associated at genome-wide significance level. For the quantitative trait, evidence of association was detected at GFRA1, a receptor for the neurotrophin GDRA (p = 2e-06). For the discrete trait of suicide attempt, SNPs in KIAA1244 and RGS18 attained p-values of <5e-6. None of these SNPs showed evidence for replication in the additional cohorts tested. Candidate gene analysis provided some support for a polymorphism in NTRK2, which was previously associated with suicidality.
This study provides a genome-wide assessment of possible genetic contribution to suicidal behaviour in depression but indicates a genetic architecture of multiple genes with small effects. Large cohorts will be required to dissect this further.
PLoS ONE 07/2011; 6(7):e20690. DOI:10.1371/journal.pone.0020690 · 3.23 Impact Factor
"Although many suicide subjects have a diagnosable psychiatric illness, most persons with a psychiatric disorder never attempt suicide . Suicidal behavior aggregates in families , and studies of twins show that monozygotic individuals have a greater concordance for suicide completion and suicide attempts compared to dizygotic individuals –. Non-genetic familial factors, including a history of abuse or neglect during childhood, are also risk factors for suicidal behavior , . "
[Show abstract][Hide abstract] ABSTRACT: Alterations in gene expression in the suicide brain have been reported and for several genes DNA methylation as an epigenetic regulator is thought to play a role. rRNA genes, that encode ribosomal RNA, are the backbone of the protein synthesis machinery and levels of rRNA gene promoter methylation determine rRNA transcription.
We test here by sodium bisulfite mapping of the rRNA promoter and quantitative real-time PCR of rRNA expression the hypothesis that epigenetic differences in critical loci in the brain are involved in the pathophysiology of suicide. Suicide subjects in this study were selected for a history of early childhood neglect/abuse, which is associated with decreased hippocampal volume and cognitive impairments. rRNA was significantly hypermethylated throughout the promoter and 5' regulatory region in the brain of suicide subjects, consistent with reduced rRNA expression in the hippocampus. This difference in rRNA methylation was not evident in the cerebellum and occurred in the absence of genome-wide changes in methylation, as assessed by nearest neighbor.
This is the first study to show aberrant regulation of the protein synthesis machinery in the suicide brain. The data implicate the epigenetic modulation of rRNA in the pathophysiology of suicide.
PLoS ONE 02/2008; 3(5):e2085. DOI:10.1371/journal.pone.0002085 · 3.23 Impact Factor
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