GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors

Objective: Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and crossvalidated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS metaanalysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures. Methods: This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses. Results: Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values &lt;5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors. Conclusions: This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.</p

GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors

OBJECTIVE: Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures. METHODS: This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses. RESULTS: Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values \u3c5×10 CONCLUSIONS: This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death

Discovery of 95 PTSD loci provides insight into genetic architecture and neurobiology of trauma and stress-related disorders

Posttraumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 novel). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (e.g., GRIA1, GRM8, CACNA1E ), developmental, axon guidance, and transcription factors (e.g., FOXP2, EFNA5, DCC ), synaptic structure and function genes (e.g., PCLO, NCAM1, PDE4B ), and endocrine or immune regulators (e.g., ESR1, TRAF3, TANK ). Additional top genes influence stress, immune, fear, and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation

Evaluation Of Photodynamic Therapy Using A Diode Laser And Different Photosensitizers Against Enterococcus Faecalis.

Photodynamic therapy (PDT) has been proven to be effective in disinfecting root canals. The aim of this present study was to evaluate the effects of PDT on the viability of Enterococcus faecalis using methylene blue (MB) and malachite green (MG) as photosensitizers. Solutions containing E. faecalis (ATCC 29212) were prepared and harvested by centrifugation to obtain cell suspensions, which were mixed with MB and MG. Samples were individually irradiated by the diode laser at a distance of 1mm for 30, 60, or 120 seconds. Colonyforming units (CFU) were determined for each treatment. PDT for 60 and 120 seconds with MG reduced E. faecalis viability significantly. Similar results were obtained when MB was used as photosensitizer. PDT using MB and MG have antibacterial effect against E. faecalis, showing potential to be used as an adjunctive antimicrobial procedure in endodontic therapy.2763-

Distribuição espacial de Mesadenella cuspidata (Lindl.) Garay (Orchidaceae) em uma floresta ribeirinha em Santa Maria, RS, Brasil Spatial distribution of Mesadenella cuspidata (Lindl.) Garay (Orchidaceae) in a riparian forest, Santa Maria, RS, Brazil

Mesadenella cuspidata é uma orquídea terrícola encontrada no interior de florestas no Sul do Brasil. Apesar de seu valor ecológico e ornamental, pouco se conhece sobre a biologia desta espécie. Os objetivos deste trabalho foram identificar o padrão de distribuição espacial de M. cuspidata e verificar se há correlação entre o número de indivíduos jovens e adultos em uma floresta ribeirinha. Para o levantamento, foram amostradas 60 parcelas de 16m² cada. Durante agosto e setembro/2001 foram inventariados os indivíduos jovens e adultos das parcelas. Para identificar-se o padrão de distribuição espacial, utilizaram-se o índice de Morisita (MI) e a razão de variância/média (R). Foram encontrados 463 indivíduos jovens e 178 adultos. Indivíduos jovens e adultos apresentaram distribuição espacial agrupada, sendo que os adultos (IM = 2,17; R = 4,52) estão mais agrupados que os jovens (IM = 1,82; R = 7,82). O coeficiente de correlação linear encontrado r = 0,61, demonstrou que a densidade de indivíduos adultos está altamente relacionada à densidade de indivíduos jovens.<br>Mesadenella cuspidata (Lindl.) Garay is a terrestrial orchid found inside Southern Brazilian forests. In spite of its ecological and ornamental value, little information is aviable on its biology. The aim of this work was the identification of the spatial distribution patterns of M. cuspidata in a riparian forest. We have sampled 60 quadrats of 16m² each. All the young and adult individuals of the quadrats were included. To identify the pattern of spatial distribution, the Morisita Index (MI) and the variance/mean Reason (R) were used. The linear correlation coefficient was used to verify if there is correlation between populations of the juvenils and adults. From 641 individuals sampled, 463 were juvenils and 178 were adults. Juvenils and adult individuals presented gregarious spatial distribution, but the adults (MI = 2,17; R = 4,52) were more gregarious than the juvenils (IM = 1,82; R = 7,82). The high relation between the densities of adults and juvenils had been demonstrated by the value of the linear correlation coefficient found, r = 0,61