Genetic relationships between suicide attempts, suicidal ideation and major psychiatric disorders: A genome‐wide association and polygenic scoring study

Mullins, Niamh; Perroud, Nader; Uher, Rudolf; Butler, Amy W.; Cohen‐Woods, Sarah; Rivera, Margarita; Malki, Karim; Euesden, Jack; Power, Robert A.; Tansey, Katherine E.; Jones, Lisa; Jones, Ian; Craddock, Nicholas John; Owen, Michael John; Korszun, Ania; Gill, Michael; Mors, Ole; Preisig, Martin; Maier, Wolfgang; Rietschel, Marcella; Rice, John P.; Müller‐Myhsok, Bertram; Binder, Elisabeth B.; Lucae, Susanne; Craig, Ian W.; Farmer, Anne; McGuffin, Peter; Breen, Gerome; Lewis, Cathryn M.

doi:10.1002/ajmg.b.32247

Cited by 111 publications

(135 citation statements)

References 51 publications

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“…* The human ortholog is NPAS4, which has been associated with dipolar disorder (Psychiatric GWAS Consortium Bipolar Disorder Working Group 2011). † The human ortholog is NCAM1, which has been associated with suicide attempts in depression and bipolar disorder (Mullins et al 2014). …”

Section: Insights About the Molecular Genetic Basis Of Natural Variatmentioning

confidence: 99%

Genomic Analysis of Genotype-by-Social Environment Interaction for Drosophila melanogaster Aggressive Behavior

et al. 2017

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Human psychiatric disorders such as schizophrenia, bipolar disorder and attention-deficit/hyper-activity disorder often include adverse behaviors including increased aggressiveness. Individuals with psychiatric disorders often exhibit social withdrawal, which can further increase the probability of conducting a violent act. Here, we used the inbred, sequenced lines of the Drosophila Genetic Reference Panel (DGRP) to investigate the genetic basis of variation in male aggressive behavior for flies reared in a socialized and socially isolated environment. We identified genetic variation for aggressive behavior, as well as significant genotype by social environmental interaction (GSEI); i.e., variation among DGRP genotypes in the degree to which social isolation affected aggression. We performed genome-wide association (GWA) analyses to identify genetic variants associated with aggression within each environment. We used genomic prediction to partition genetic variants into gene ontology (GO) terms and constituent genes, and identified GO terms and genes with high prediction accuracies in both social environments and for GSEI. The top predictive GO terms significantly increased the proportion of variance explained, compared to prediction models based on all segregating variants. We performed genomic prediction across environments, and identified genes in common between the social environments which turned to be enriched for genome-wide associated variants.A large proportion of the associated genes have previously been associated with aggressive behavior in Drosophila and mice.Further, many of these genes have human orthologs that have been associated with neurological disorders, indicating partially shared genetic mechanisms underlying aggression in animal models and human psychiatric disorders.

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Section: Insights About the Molecular Genetic Basis Of Natural Variatmentioning

confidence: 99%

Genomic Analysis of Genotype-by-Social Environment Interaction for Drosophila melanogaster Aggressive Behavior

et al. 2017

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“…Finally, Mullins et al (2014) is the most recent GWAS in this category. The samples for suicide attempts were the same as in Schosser et al (2011) supplemented with another sample, and for TWOSI/TESI outcomes it was the sample of Perroud et al (2012).…”

Section: Suicidal Behavior Outcomesmentioning

confidence: 99%

Genome-wide association studies of suicidal behaviors: A review

Sokolowski

Wasserman

2014

European Neuropsychopharmacology

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“…Five GWAS of suicide attempt have been reported [12-16]. The acid phosphatase ( ACP1 ) gene reported in a GWAS of suicide attempt in bipolar disorder has recently been replicated in a sample of schizophrenia patients [17].…”

Section: Introductionmentioning

confidence: 99%

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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Genetic relationships between suicide attempts, suicidal ideation and major psychiatric disorders: A genome‐wide association and polygenic scoring study

Cited by 111 publications

References 51 publications

Genomic Analysis of Genotype-by-Social Environment Interaction for Drosophila melanogaster Aggressive Behavior

Genomic Analysis of Genotype-by-Social Environment Interaction for Drosophila melanogaster Aggressive Behavior

Genome-wide association studies of suicidal behaviors: A review

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

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