Suicide behavior as a quantitative trait and its genetic background

J Affect Disord. 2016 Dec;206:241-250. doi: 10.1016/j.jad.2016.07.029. Epub 2016 Jul 19.

Abstract

Introduction: Studies have not given yet a clear answer what is the genetic background of suicidal predisposition. The associations between polymorphisms of the TPH1 and 5-HTTLPR genes and violent suicidal behavior was revealed with the least inconsistencies.

Method: We selected 10 "strong candidate genes" and 35 SNPs, SLC6A4 and ACP1 for replication study. We searched associations between precisely described suicidal phenotype in 825 affective patients and polymorphisms of selected neurobiological pathways genes as well as their interactions that constitute suicidal risk.

Results: The results confirm the role of TPH1, TPH2, 5HT2A, CRHR1 and ACP1 variants in the risk of suicidal behavior.

Limitations: In our study we analyzed limited number of candidate genes and only one of them is linked to lithium mechanism of action. We had no data on pharmacological treatment of investigated patients and its relation to the time of suicide attempt.

Conclusion: Our results indicate that polymorphisms of various signaling pathways are involved in the pathogenesis of suicidal behavior. Non-genetic factors are also involved in the risk of suicidal attempts.

Keywords: Association study; Gene-gene interaction; Quantitative trait; Suicide attempt.

MeSH terms

  • Adolescent
  • Adult
  • Bipolar Disorder / genetics
  • Case-Control Studies
  • Depressive Disorder, Major / genetics
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease / genetics
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Phenotype
  • Polymorphism, Single Nucleotide / genetics
  • Protein Tyrosine Phosphatases / genetics*
  • Proto-Oncogene Proteins / genetics*
  • Receptor, Serotonin, 5-HT2A / genetics*
  • Receptors, Corticotropin-Releasing Hormone / genetics*
  • Serotonin Plasma Membrane Transport Proteins / genetics
  • Suicidal Ideation*
  • Suicide / psychology
  • Suicide, Attempted / psychology*
  • Tryptophan Hydroxylase / genetics*
  • Young Adult

Substances

  • Proto-Oncogene Proteins
  • Receptor, Serotonin, 5-HT2A
  • Receptors, Corticotropin-Releasing Hormone
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • CRF receptor type 1
  • TPH1 protein, human
  • TPH2 protein, human
  • Tryptophan Hydroxylase
  • ACP1 protein, human
  • Protein Tyrosine Phosphatases