Some practical thoughts about suicide: Before jumping, you should consult your genes

January 21, 2017 –There are roughly one million suicides worldwide annually, corresponding to an estimated yearly mortality rate of 14.5 deaths per 100,000 people in the general population. In Europe, suicide represents the second leading cause of mortality in the 14–24 age groups. Suicide constitutes a multifactorial public health issue that involves numerous biological, psychological, cultural, social, and family determinants. Support for the implication of genetic risk factors in suicidal behavior (SB) is provided by studies of families, twins, and adoption cases. Studies of adoption have also shown that there is a higher risk of suicide for the individuals who are biologically related to suicidal probands, but not for non-biologically related members of adoptive families. The recent findings of a large body of studies suggest significant heritability (h2) of completed suicide, with an aggregate estimate of h2 = 45%. The heritability appears to depend in part on psychiatric disorders such as mood disorders and substance abuse, with ~90% of suicide attempters having a psychiatric disorder, and, importantly, to also be partly independent of them. This independent factor has been hypothesized to influence impulsive aggression, with individuals who have both of these personality traits and a major mental disorder having the greatest risk of SB.

The following recent review article by B. Mirkovic et al., entitled “Genetic Association Studies of Suicidal Behavior: A Review of the Past 10 Years, Progress, Limitations, and Future Directions” gives a comprehensive overview on what we know today on the influence of our genes on suicidal behaviour (SB) and even completion of suicide.

We think that this article is worthwhile to read for the general public and particularly also for people at risk. It may help the latter to better understand their condition and to adjust behaviours and therapeutic options accordingly. We give here the unedited abstract of the article, which can be found here in full.

Abstract: Suicidal behaviors (SBs), which range from suicidal ideation to suicide attempts and completed suicide, represent a fatal dimension of mental ill-health. The involvement of genetic risk factors in SB is supported by family, twin, and adoption studies. The aim of this paper is to review recent genetic association studies in SBs including (i) case–control studies, (ii) family-based association studies, and (iii) genome-wide association studies (GWAS). Various studies on genetic associations have tended to suggest that a number of genes [e.g., tryptophan hydroxylase, serotonin receptors and transporters, or brain-derived neurotrophic factors (BDNFs)] are linked to SBs, but these findings are not consistently supported by the results obtained. Although the candidate–gene approach is useful, it is hampered by the present state of knowledge concerning the pathophysiology of diseases. Interpretations of GWAS results are mostly hindered by a lack of annotation describing the functions of most variation throughout the genome. Association studies have addressed a wide range of single-nucleotide polymorphisms in numerous genes. We have included 104 such studies, of which 10 are family-based association studies and 11 are GWAS. Numerous meta-analyses of case–control studies have shown significant associations of SB with variants in the serotonin transporter gene (5-HTT or SLC6A4) and the tryptophan hydroxylase 1 gene (TPH1), but others report contradictory results. The gene encoding BDNF and its receptor (NTRK2) are also promising candidates. Only two of the GWAS showed any significant associations. Several pathways are mentioned in an attempt to understand the lack of reproducibility and the disappointing results. Consequently, we review and discuss here the following aspects: (i) sample characteristics and confounding factors; (ii) statistical limits; (iii) gene–gene interactions; (iv) gene, environment, and by time interactions; and (v) technological and theoretical limits.

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About the Author
Joseph Gut - thasso Ph.D.; Professor in Pharmacology and Toxicology. Senior expert in theragenomic and personalized medicine and individualized drug safety. Senior expert in pharmaco- and toxicogenetics. Senior expert in human safety of drugs, chemicals, environmental pollutants, and dietary ingredients.

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