Analysis of Four Genes Involved in the Neurodevelopment Shows Association of rs4307059 Polymorphism in the Cadherin 9/10 Region with Completed Suicide

Abstract

Background: We hypothesized that DNA variants affecting neurodevelopment such as rs4307059 (CDH10/CDH9), rs930752 (NRXN1), rs6265 (BDNF) or rs10868235 (NTRK2) may predispose to completed suicide. Methodology: We used a case-control two-stage approach based on a discovery cohort (557 cases and ∼550 controls) and replication cohort (159 cases and 186 controls). The suicides were ascertained as consecutive cases autopsied at the Department of Forensic Medicine, Medical University of Warsaw, Poland. Results: In the discovery cohort we found an association between suicide and the CC genotype in the rs4307059 polymorphism (OR 1.64, p = 0.012). The trend for an overrepresentation of the CC homozygotes among suicides was replicated in the second cohort (OR 1.97, p = 0.056). Analysis in the pooled cohorts showed that rs4307059 CC was associated with completed suicide (OR 1.71, p = 0.002) also after Bonferroni correction (p_cor. = 0.024). In an exploratory search for genotype-phenotype correlation we found that males with the rs4307059 CC genotype committed suicide earlier than those with CT/TT genotypes (p = 0.049). Conclusions: The CC genotype of rs4307059 located in the region between CDH9 and CDH10 is associated with completed suicide in a Polish cohort.

A Novel Relationship for Schizophrenia, Bipolar, and Major Depressive Disorder. Part 8: a Hint from Chromosome 8 High Density Association Screen

“…(2) CDH9 ( Table 2, 12 & Supplementary Table 1, 4,063-4,379) is strongly expressed in the fetal brain and parietal lobe of the brain. This gene was reported to be associated with antidepressants [23], BPD [22], suicide [24], and autism [25]. One downstream SNP (rs1004-5680) and three upstream SNPs (rs1508177, rs1552007, rs182728) were found to be associated with SCZ and BPD respectively in this study ( Table 2, [9][10][11][12].…”

The role of childhood adversities, FKBP5, BDNF, NRN1, and generalized self-efficacy in suicide attempts in alcohol-dependent patients

“…Carriers of the BDNF rs6265 66Met (A) allele and male sex were predictors of high lethality in suicide attempts in 120 patients with major depressive disorder (MDD) [ 60 ]. A post-mortem study conducted by Chojnicka et al [ 29 ] found no association between BDNF rs6265 and suicide in 557 autopsied suicide victims in a heterogenous population, including 181 individuals with a confirmed history of psychiatric disorder (i.e., depression, schizophrenia, other unknown) and alcohol and/or drug addiction. Kohli et al [ 61 ] found an association between BDNF rs6265 and suicide attempt in 394 MDD patients from the German population.…”

“…Plasma levels of BDNF were also lower in suicidal depressed patients when compared to non-suicidal depressed subjects [ 27 , 28 ]. In contrast, a post-mortem study found no association between BDNF rs6265 and suicide among a sample of 181 autopsied suicide victims with a history of alcohol and/or drug addiction [ 29 ].…”

Association of HTTLPR, BDNF, and FTO Genetic Variants with Completed Suicide in Slovakia

“…Our results are in accordance with a meta-analysis study in which a significant association between BDNF rs6265 polymorphism and the risk of suicidal behavior in the overall population was not confirmed [ 14 ]. This meta-analysis included studies from three populations of Slavic origin (Croatia, Slovenia, and Poland), out of which three did not confirm any association [ 33 , 34 , 35 ], and one found a higher risk for carriers of at least one minor allele (Met-Met or Val-Met) but only in female suicide victims [ 36 ]. Neither the more recent study from Central Europe [ 37 ] nor an earlier European multicenter study [ 38 ] has found an association between rs6365 and suicidal behavior.…”