Genome-wide association studies of suicidal behaviors

Résumé

A general genetic diathesis of suicidality has been shown to exist by family, adoption, and twin studies, with heritability in the range between 30 and 55% (Voracek & Loibl, 2007). Such a general genetic diathesis mainly refers to the behavioral manifestations of suicidality (i.e., suicide attempts or completed suicides), rather than suicidal thoughts or ideation alone. However, this is not clear-cut, as ideation precedes a proportion of suicide attempts or completed suicides (Baca-Garcia et al., 2011). Specific genetic components (i.e., particular candidate genes) are therefore often being studied, i.e. genes which are implicated in suicidality or its associated psychopathologies on the basis of prior biological and/or pharmacological knowledge and observations (Currier & Mann, 2008; Wasserman et al., 2009). Selected genetic variants in serotonergic system genes have been the major historic focus of such investigations during the past decades, but the polygenetic perspective is nowadays also being addressed by, for example, the study of candidate genes in other neurosystems (Wasserman et al., 2005, 2007, 2008, 2009; Ernst et al., 2009; Rujescu & Giegling, 2010; Sokolowski et al., 2010, 2012; Ben-Efraim et al., 2011, 2112, 2013). A relatively novel approach for further elucidating the polygenetic perspective, which has become available in the last years, is to conduct a Genome-Wide Association Study (GWAS). GWAS is a concept whereby many genetic markers across the whole genome are simultaneously analyzed for association with a trait (Ikegawa, 2012). It has been termed as a hypothesis-free approach (with regard to that any of the markers/genes are being hypothesized to show association), which is in contrast to the candidate gene approach (Goldstein et al., 2003). One main goal of GWAS is to suggest novel candidate genes which could not be hypothesized a priori by current knowledge. In the end, there are no simple answers to the inherently complex question about the genetics of suicidality. But it is clear that GWAS have lots of potential to provide some of the answers, which can ultimately be translated into better understanding and improvement of prevention, intervention, and treatment options for suicidal behaviors. (PsycINFO Database Record (c) 2015 APA, all rights reserved) GÉNÉTIQUE