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Investigation of the genetic interaction between BDNF and DRD3 genes in suicidical behaviour in psychiatric disorders.

ABSTRACT: OBJECTIVES:Suicide is a serious public health concern, and it is partly genetic. The brain-derived neurotrophic factor (BDNF) gene has been a strong candidate in genetic studies of suicide (Dwivedi et al., Arch Gen Psychiatry 2010;60:804-815; Zai et al., Prog Neuropsychopharmacol Biol Psychiatry 2012;34:1412-1418) and BDNF regulates the expression of the dopamine D3 receptor. OBJECTIVE:We examined the role of the BDNF and DRD3 genes in suicide. METHODS:We analysed four tag single-nucleotide polymorphisms (SNPs) in BDNF and 15 SNPs in the D3 receptor gene DRD3 for possible association with suicide attempt history in our Canadian sample of Schizophrenia (SCZ) patients of European ancestry (N = 188). RESULTS:In this sample, we found a possible interaction between the BDNF Val66Met and DRD3 Ser9Gly SNPs in increasing the risk of suicide attempt(s) in our SCZ sample. Specifically, a larger proportion of SCZ patients who were carrying at least one copy of the minor allele at each of the Val66Met and Ser9Gly functional markers have attempted suicides compared to patients with other genotypes (Bonferroni P < 0.05). However, we could not replicate this finding in samples from other psychiatric populations. CONCLUSIONS:Taken together, the results from the present study suggest that an interaction between BDNF and DRD3 may not play a major role in the risk for suicide attempt, though further studies, especially in SCZ, are required.

SUBMITTER: Zai CC

PROVIDER: S-EPMC4377309 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Investigation of the genetic interaction between BDNF and DRD3 genes in suicidical behaviour in psychiatric disorders.

Zai Clement C CC Manchia Mirko M Sønderby Ida Elken IE Yilmaz Zeynep Z De Luca Vincenzo V Tiwari Arun K AK Squassina Alessio A Zai Gwyneth C GC Shaikh Sajid A SA Strauss John J King Nicole N Le Foll Bernard B Kaplan Allan S AS Finseth Per I PI Vaaler Arne E AE Djurovic Srdjan S Andreassen Ole A OA Vincent John B JB Kennedy James L JL

The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry 20140929 3

<h4>Objectives</h4>Suicide is a serious public health concern, and it is partly genetic. The brain-derived neurotrophic factor (BDNF) gene has been a strong candidate in genetic studies of suicide (Dwivedi et al., Arch Gen Psychiatry 2010;60:804-815; Zai et al., Prog Neuropsychopharmacol Biol Psychiatry 2012;34:1412-1418) and BDNF regulates the expression of the dopamine D3 receptor.<h4>Objective</h4>We examined the role of the BDNF and DRD3 genes in suicide.<h4>Methods</h4>We analysed four tag ...[more]

PMID: 25264289

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Project description:Background: Suicidal behaviour (SB) refers to behaviours, ranging from non-fatal suicidal behaviour, such as suicidal ideation and attempt, to completed suicide. Despite recent advancements in genomic technology and statistical methods, it is unclear to what extent the spectrum of suicidal behaviour is explained by shared genetic aetiology. Methods: We identified nine genome-wide association statistics of suicidal behaviour (sample sizes, n, ranging from 62,648 to 125,844), ten psychiatric traits [n up to 386,533] and collectively, nine summary datasets of anthropometric, behavioural and socioeconomic-related traits [n ranging from 58,610 to 941,280]. We calculated the genetic correlation among these traits and modelled this using genomic structural equation modelling, identified shared biological processes and pathways between suicidal behaviour and psychiatric disorders and evaluated potential causal associations using Mendelian randomisation. Results: Among populations of European ancestry, we observed strong positive genetic correlations between suicide ideation, attempt and self-harm (rg range, 0.71-1.09) and moderate to strong genetic correlations between suicidal behaviour traits and a range of psychiatric disorders, most notably, major depression disorder (rg = 0.86, p = 1.62 × 10-36). Multivariate analysis revealed a common factor structure for suicidal behaviour traits, major depression, attention deficit hyperactivity disorder (ADHD) and alcohol use disorder. The derived common factor explained 38.7% of the shared variance across the traits. We identified 2,951 genes and 98 sub-network hub genes associated with the common factor, including pathways associated with developmental biology, signal transduction and RNA degradation. We found suggestive evidence for the protective effects of higher household income level on suicide attempt [OR = 0.55 (0.44-0.70), p = 1.29 × 10-5] and while further investigation is needed, a nominal significant effect of smoking on suicide attempt [OR = 1.24 (1.04-1.44), p = 0.026]. Conclusion: Our findings provide evidence of shared aetiology between suicidal behaviour and psychiatric disorders and indicate potential common molecular mechanisms contributing to the overlapping pathophysiology. These findings provide a better understanding of the complex genetic architecture of suicidal behaviour and have implications for the prevention and treatment of suicidal behaviour.

Dataset Information

Investigation of the genetic interaction between BDNF and DRD3 genes in suicidical behaviour in psychiatric disorders.

Publications

Investigation of the genetic interaction between BDNF and DRD3 genes in suicidical behaviour in psychiatric disorders.

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