A genome-wide association study of suicide severity scores in bipolar disorder

Zai, Clement C.; Gonçalves, Vanessa F.; Tiwari, Arun K.; Gagliano, Sarah A.; Hosang, Georgina M.; Luca, Vincenzo De; Shaikh, Sajid; King, Nicole; Chen, Qian; Xu, Wei; Strauss, John S.; Breen, Gerome; Lewis, Cathryn M.; Farmer, Anne; McGuffin, Peter; Knight, Jo; Vincent, John B.; Kennedy, James L.

doi:10.1016/j.jpsychires.2014.11.002

Cited by 37 publications

(35 citation statements)

References 36 publications

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“…We attempted to replicate the TGFRB1 findings from this study using available GWAS data from a replication bipolar disorder sample that was collected from the Institute of Psychiatry in London, UK [22, 23]. The TGFBR1 gene was not significant in the gene-based analysis in the replication sample.…”

Section: Resultsmentioning

confidence: 99%

“…Suicidal behavior severity was assessed for the lifetime worst depressive episode by the interviewer using the SCAN Suicide Severity item, with 0 meaning nonsuicidal ( n = 71), 1 denoting suicidal ideation/plan ( n = 78), 2 denoting suicide attempt without serious harm ( n = 37), 3 indicating suicide attempt with serious harm ( n = 11), and 4 indicating suicide attempt aiming to end life ( n = 22). The self-reported European ancestry of the sample was validated with GWAS data from a previous study [23] and is briefly described for the replication sample below.…”

Section: Methodsmentioning

confidence: 99%

“…The replication bipolar disorder sample was collected from the Institute of Psychiatry, London, UK, with the same protocol as our discovery sample [22, 23]. The replication sample consisted of 362 patients of European ancestry (average age 47.03 ± 11.10 years; 119 males and 243 females).…”

Section: Methodsmentioning

confidence: 99%

“…These patients were genotyped on the Illumina HumanHap550 Beadchip at Illumina as described previously [22]. Genotype quality control strategies were described in our GWAS of suicidal behavior severity [23]. Briefly, we applied quality control measures using PLINK (a whole-genome association studies tool set) [26] and R (R Development Core Team, 2008).…”

Section: Methodsmentioning

confidence: 99%

“…Covariates included a large number (at least 40) of depressive episodes [29, 30], age, sex, lifetime alcohol (ever drank at least 5 alcoholic drinks every day) [31-33], and the first 2 principal components from the population structure analysis described previously [23]. We used gene- or region-based analysis of variants of intermediate and low frequency to conduct gene-based analysis [34], first involving all variants in each gene region and then involving only variants with a minor allele frequency of < 5%.…”

Section: Methodsmentioning

confidence: 99%

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Sequence Analysis of Drug Target Genes with Suicidal Behavior in Bipolar Disorder Patients

Tiwari

Luca

et al. 2018

Complex Psychiatry

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Background: A number of genes have been implicated in recent genome-wide association studies of suicide attempt in bipolar disorder. More focused investigation of genes coding for protein targets of existing drugs may lead to drug repurposing for the treatment and/or prevention of suicide. Methods: We analyzed 2,457 DNA variants across 197 genes of interest to GlaxoSmithKline across the pipeline in our sample of European patients suffering from bipolar disorder (N = 219). We analyzed these variants for a possible association with the suicide severity score (ranging from suicidal ideation/plan to serious suicide attempt) from the Schedule for Clinical Assessment in Neuropsychiatry. We conducted tests of individual variants and gene-based tests. Results: We found a number of DNA variants in the transforming growth factor beta receptor 1 gene (TGFBR1) to be suggestively associated with suicide severity scores (p < 0.005). The gene-based tests also pointed to TGFBR1 to be associated with suicide severity (p = 0.0001). However, these findings were not replicated in an independent bipolar disorder sample. Conclusions: We report no significant association between DNA sequences of drug target genes and suicidal behavior. Additional larger sequencing studies could further interrogate associations between variants in drug target genes and suicidal behavior.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Sequence Analysis of Drug Target Genes with Suicidal Behavior in Bipolar Disorder Patients

Tiwari

Luca

et al. 2018

Complex Psychiatry

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Genetics of Suicidality

Blackman

Lasky‐Su

2017

Encyclopedia of Life Sciences

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Suicide is the 15th leading cause of death, making it a serious public health problem. While external life influences tend to be the focus of why suicide attempts occur, there is consistent evidence that underlying genetic determinants contribute substantially to suicidal ideation. In this article, we first review the general epidemiology of suicide and then discuss the various ways genetic determinants result in suicidal ideation, suicide attempts and suicide itself. Specifically, we discuss how other psychiatric illnesses, including depression, bipolar disorder, alcoholism and schizophrenia are comorbid with suicidality, thereby making the genetic determinants for these other psychiatric conditions also genetic risk factors for suicidality. We do this by reviewing the current genetic research findings from these psychiatric conditions and link the findings to suicidality. Key Concepts Suicidality is a complex disease that is a result of both genetic and environmental influences. Suicidality often cooccurs with other psychiatric conditions. There is often an environmental trigger, which, in conjunction with a genetic predisposition, can result in suicide attempts. Several of the genetic underpinnings for other psychiatric disorders are likely also associated with suicidality. More research is necessary to identify and confirm genetic variants for suicidality.

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Identification of gene ontology and pathways implicated in suicide behavior: Systematic review and enrichment analysis of GWAS studies

González‐Castro

Tovilla‐Zárate

Genis‐Mendoza

et al. 2019

American J of Med Genetics Pt B

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Multiple large-scale studies such as genome-wide association studies (GWAS) have been performed to identify genetic contributors to suicidal behaviors (SB). We aimed to summarize and analyze the information obtained in SB GWAS, to explore the biological process gene ontology (GO) of genes associated with SB from GWAS, and to determine the possible implications of the genes associated with SB in Kyoto encyclopedias of genes and genomes (KEGG) biological pathways. The articles included in the analysis were obtained from PubMed and Scopus databases. Enrichment analyses were performed in Enrichr to evaluate the KEGG pathways and GO of the genes associated with SB of GWAS. The findings of biological process GO analysis showed 924 GO involved in genes related with SB; of those, the regulation of glucose import in response to insulin stimulus, regulation of protein localization to plasma membrane, positive regulation of endopeptidase activity, heterotypic cell-cell adhesion, regulation of cardiac muscle cell contraction, positive regulation of protein localization to plasma membrane, and positive regulation of protein localization to cell periphery biological process GO showed significant statistical association. Furthermore, we obtained 130 KEGG pathways involved in genes related with SB, which Aldosterone synthesis and secretion, Rap1 signaling pathway and arrhythmogenic right ventricular cardiomyopathy pathways showed a significant statistical association. These findings give a better perspective of the biological participation of genes associated with SB, which will be important to perform adequate strategies to prevent and treat SB.

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A genome-wide association study of suicide severity scores in bipolar disorder

Abstract: Our GWAS findings suggest that likely many gene variants of small effects contribute collectively to the risk for suicidal behaviour severity in BD. Larger independent replications are required to strengthen the findings from the GWAS presented here.

Cited by 37 publications

References 36 publications

Sequence Analysis of Drug Target Genes with Suicidal Behavior in Bipolar Disorder Patients

Sequence Analysis of Drug Target Genes with Suicidal Behavior in Bipolar Disorder Patients

Genetics of Suicidality

Identification of gene ontology and pathways implicated in suicide behavior: Systematic review and enrichment analysis of GWAS studies

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