Recent molecular genetic studies and methodological issues in suicide research

Suicide behavior (SB) spans a spectrum ranging from suicidal ideation to suicide attempts and completed suicide. Strong evidence suggests a genetic susceptibility to SB, including familial heritability and common occurrence in twins. This review addresses recent molecular genetic studies in SB that include case–control association, genome gene-expression microarray, and genome-wide association (GWA). This work also reviews epigenetics in SB and pharmacogenetic studies of antidepressant-induced suicide.SB fulfills criteria for a complex genetic phenotype in which environmental factors interact with multiple genes to influence susceptibility. So far, case–control association approaches are still the mainstream in SB genetic studies, although whole genome gene-expression microarray and GWA studies have begun to emerge in recent years. Genetic association studies have suggested several genes (e.g., serotonin transporter, tryptophan hydroxylase 2, and brain-derived neurotrophic factor) related to SB, but not all reports support these findings. The case–control approach while useful is limited by present knowledge of disease pathophysiology. Genome-wide studies of gene expression and genetic variation are not constrained by our limited knowledge. However, the explanatory power and path to clinical translation of risk estimates for common variants reported in genome-wide association studies remain unclear because of the presence of rare and structural genetic variation. As whole genome sequencing becomes increasingly widespread, available genomic information will no longer be the limiting factor in applying genetics to clinical medicine. These approaches provide exciting new avenues to identify new candidate genes for SB genetic studies. The other limitation of genetic association is the lack of a consistent definition of the SB phenotype among studies, an inconsistency that hampers the comparability of the studies and data pooling.In summary, SB involves multiple genes interacting with non-genetic factors. A better understanding of the SB genes by combining whole genome approaches with case–control association studies, may potentially lead to developing effective screening, prevention, and management of SB.

Research Highlights
► Genetic association studies have suggested several genes (e.g., serotonin transporter, tryptophan hydroxylase 2, and brain-derived neurotrophic factor) related to SB, but not all reports support these findings.
► The major limitation of genetic association is the lack of a consistent definition of the SB phenotype among studies.
► Genome-wide studies of gene expression and genetic variation are not constrained by our limited knowledge.