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  1. Article ; Online: A candidate biological network formed by genes from genomic and hypothesis-free scans of suicide.

    Sokolowski, Marcus / Wasserman, Danuta

    Preventive medicine

    2021  Volume 152, Issue Pt 1, Page(s) 106604

    Abstract: Information about genes and the biology of suicidal behavior (SB) is noisy due to heterogenous outcomes (suicide attempts or deaths), as well as many different genes and overlapping biological processes implicated. One approach to test the unbiased ... ...

    Abstract Information about genes and the biology of suicidal behavior (SB) is noisy due to heterogenous outcomes (suicide attempts or deaths), as well as many different genes and overlapping biological processes implicated. One approach to test the unbiased biological coherence of disease genes, is to use genes from hypothesis-free genetic scans and to investigate if they aggregate close to each other in cellular gene and protein interaction networks ("interactomes"). Therefore, we used network methods to study the biological coherence among genes (n = 229) from genome-wide association studies (GWAS) and whole exome sequencing (WES) of suicide outcome. Results showed that the suicide GWAS+WES genes has significant aggregation in three major interactome database assemblies, a hallmark of biological similarity and increased likelihood of being involved in the same outcome (suicide). This pinpointed e.g. genes on chromosome 19, which are also associated with lipid metabolism, schizophrenia and bipolar disorder. We identified a subset of GWAS+WES "core" genes (n = 54) which are the most proximal to each other in the context of three interactome assemblies, and present a candidate network module of suicide which is specific for nervous system tissues. The n = 54 most proximal "core" genes showed overrepresentation of synaptic and nervous system development genes, as well as network paths to other SB genes having increased evidence diversity. Overall, results suggested the existence of a coherent biology in suicide outcome and provide unbiased biological support concerning links to other SB genes, as well as e.g. bipolar disorder, excitatory/inhibitory function and ketamine treatment in SB.
    MeSH term(s) Genome-Wide Association Study ; Genomics ; Humans ; Schizophrenia/genetics ; Suicidal Ideation ; Suicide, Attempted
    Language English
    Publishing date 2021-09-16
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 184600-0
    ISSN 1096-0260 ; 0091-7435
    ISSN (online) 1096-0260
    ISSN 0091-7435
    DOI 10.1016/j.ypmed.2021.106604
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  2. Article ; Online: Accident or suicide? Improvement in the classification of suicides among road traffic fatalities in Sweden by extended psychosocial investigations, during the years 2010-2019.

    Andersson, Anna-Lena / Sokolowski, Marcus

    Journal of safety research

    2021  Volume 80, Page(s) 39–45

    Abstract: Introduction: Suicide is the second leading cause of death in the ages 15-29 worldwide, exceeded only by road injury. However, fatalities in road traffic may be either accidents or suicides. In 2010 Sweden began efforts to separately report deaths in ... ...

    Abstract Introduction: Suicide is the second leading cause of death in the ages 15-29 worldwide, exceeded only by road injury. However, fatalities in road traffic may be either accidents or suicides. In 2010 Sweden began efforts to separately report deaths in road traffic as either accidents or suicides.
    Method: Three alternative criteria defining what constitutes a fatality by suicide were introduced. After exclusion of natural deaths, fatalities were also classified on a five-level graded scale, which distinguished between accident, undetermined, and suicide. The investigations of fatalities were complemented by extended psychosocial investigations in 2012. The improvement in the classification of suicide deaths was evaluated by an intra-year 2012 comparison, as well as using the 2010-2012 period as a control to evaluate the continued use of extended psychosocial investigations during the 2013-2019 period.
    Results: The 2012 intra-year comparison showed a 63% increase in the number of identified suicides when using extended psychosocial investigations. The additional 14 suicides identified in 2012 were mainly attributed to a resolution of 12 "undetermined" causes of deaths. Suicides of all road fatalities increased from 5.7-6.8% in 2010-2011, to 11.2% in 2012. Over the subsequent period 2013-2019 with extended psychosocial investigations, suicides of all road fatalities averaged 10%, a 60% increase over prior years. An average of ∼9 additional suicides was identified each year during 2013-2019, which was accompanied by an annual reduction of ∼6 "undetermined" fatalities.
    Conclusion: The use of extended psychosocial investigations is of major importance for our knowledge about the occurrence of suicides in road traffic. Practical applications: A standardized and in-depth classification of suicide deaths is a basic prerequisite needed for the cooperation, implementation, and effect-evaluations of suicide intervention and prevention efforts, with potential to include the entire Swedish transportation system.
    MeSH term(s) Accidents ; Accidents, Traffic ; Adolescent ; Adult ; Cause of Death ; Humans ; Suicide ; Sweden/epidemiology ; Transportation ; Young Adult
    Language English
    Publishing date 2021-11-30
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2015321-1
    ISSN 1879-1247 ; 0022-4375
    ISSN (online) 1879-1247
    ISSN 0022-4375
    DOI 10.1016/j.jsr.2021.11.004
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  3. Article ; Online: A pilot study evaluating the preventive effects of platform-end lengthwise fencing on trespassing, person struck by train and traffic delays.

    Fredin-Knutzén, Johan / Hadlaczky, Gergö / Wigren, Anders / Sokolowski, Marcus

    Journal of safety research

    2023  Volume 88, Page(s) 78–84

    Abstract: Background: Trespassing at train tracks and "person under train" (PUT) incidents are serious health, societal and transportation concerns. There is a need for developing different measures to prevent these events. Here, we hypothesized that platform-end ...

    Abstract Background: Trespassing at train tracks and "person under train" (PUT) incidents are serious health, societal and transportation concerns. There is a need for developing different measures to prevent these events. Here, we hypothesized that platform-end lengthwise fences (PLF) reduce trespassing, the number of PUT incidents (suicides and accidents), and train traffic delays.
    Method: PLFs were installed as the intervention at one station in Stockholm in 2020. The number of trespassers detected using CCTV-cameras was compared before and after at the intervention station over a total period of 29 months (using incidence rate ratio, IRR). The reduction in the number of PUT (over 20 years) and train traffic delays (over 9 years) was also investigated by IRR, and by using three control groups.
    Results: After installation of PLF there was a significant ∼90% reduction in trespasses (IRR = 0.10, 95%CI 0.04-0.23; one-sided exact p < 0.0001). No PUT incident occurred at the intervention station after the installation, compared to 1.11 per year before installation (IRR = 0.32, 95%CI 0-1.82; one-sided exact p = 0.1216). There was a significant reduction in delay minutes post installation compared to before the installation (Mann Whitney U = 0, upper one-sided exact p = 0.0357). The effect of the PLF was also observable in comparison to the three control groups, suggesting that the preventive effect was not due to wider societal events affecting all stations.
    Conclusion: PLF had a large effect on reducing the number of trespasses and the number of delay minutes due to trespasses and PUT incidents. PLF may also have an effect of reducing PUT incidents.
    Practical applications: PLF is deemed to be relatively easy and cheap to install and thus scalable (as compared to full barriers, e.g., platform screen doors) and may be considered at platform-ends having an exit, provided there is enough space to install them.
    MeSH term(s) Humans ; Suicide ; Suicide Prevention ; Pilot Projects ; Railroads ; Transportation
    Language English
    Publishing date 2023-11-25
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2015321-1
    ISSN 1879-1247 ; 0022-4375
    ISSN (online) 1879-1247
    ISSN 0022-4375
    DOI 10.1016/j.jsr.2023.10.010
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  4. Article ; Online: Corrigendum to "Genetic origins of suicidality? A synopsis of genes in suicidal behaviours, with regard to evidence diversity, disorder specificity and neurodevelopmental brain transcriptomics [European Neuropsychopharmacology 37 (2020) 1-11]".

    Sokolowski, Marcus / Wasserman, Danuta

    European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology

    2020  Volume 41, Page(s) 169–171

    Language English
    Publishing date 2020-10-20
    Publishing country Netherlands
    Document type Published Erratum
    ZDB-ID 1082947-7
    ISSN 1873-7862 ; 0924-977X
    ISSN (online) 1873-7862
    ISSN 0924-977X
    DOI 10.1016/j.euroneuro.2020.10.003
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  5. Article ; Online: Genetic origins of suicidality? A synopsis of genes in suicidal behaviours, with regard to evidence diversity, disorder specificity and neurodevelopmental brain transcriptomics.

    Sokolowski, Marcus / Wasserman, Danuta

    European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology

    2020  Volume 37, Page(s) 1–11

    Abstract: With regard to suicidal behavior (SB) genetics, many novel genes have been implicated over the years, in particular by a variety of hypothesis-free genomic methods (e.g. GWAS and exome sequencing). In addition, many novel SB gene findings appear ... ...

    Abstract With regard to suicidal behavior (SB) genetics, many novel genes have been implicated over the years, in particular by a variety of hypothesis-free genomic methods (e.g. GWAS and exome sequencing). In addition, many novel SB gene findings appear enigmatic in their biological relevance and have weak statistical support, e.g. lack direct replications. Adding to this is the comorbidity between psychiatric disorders and SB. Here we provide a synopsis of SB genes, by prioritization of 106 (out of ~2500) genes based on their highest level of evidence diversity across mainly five genetic evidence types (candidate/GWAS SNP, CNV, linkage and whole exome sequencing), supplemented by three functional categories. This is a representative set of both old and new SB gene candidates, implicated by all kinds of evidence. Furthermore, we define a subset of 40 SB "specific" genes, which are not found among ~3900 genes implicated in other neuropsychiatric disorders, e.g. Autism spectrum disorders (ASD) or Schizophrenia. Biological research of suicidality contains a major developmental focus, e.g. with regard to the gene-environment interactions and epigenetic effects during childhood. Less is known about early (fetal) development and SB genes. Inspired by huge efforts to understand the role early (fetal) neurodevelopment in e.g. ASD by using brain transcriptomic data, we here also characterize the 106 SB genes. We find interesting spatiotemporal expression differences and similarities between SB specific and non-specific genes during brain neurodevelopment. These aspects are of interest to investigate further, to better understand and counteract the genetic origins suicidality.
    MeSH term(s) Brain/growth & development ; Child ; Child Development/physiology ; Fetal Development ; Gene Regulatory Networks/genetics ; Humans ; Neurodevelopmental Disorders/complications ; Neurodevelopmental Disorders/genetics ; Neurodevelopmental Disorders/psychology ; Suicidal Ideation ; Suicide/psychology ; Suicide, Attempted/psychology ; Transcriptome/genetics
    Language English
    Publishing date 2020-07-04
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 1082947-7
    ISSN 1873-7862 ; 0924-977X
    ISSN (online) 1873-7862
    ISSN 0924-977X
    DOI 10.1016/j.euroneuro.2020.06.002
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  6. Article ; Online: A pilot study evaluating the effectiveness of preventing railway suicides by mid-track fencing, which restrict easy access to high-speed train tracks.

    Fredin-Knutzén, Johan / Hadlaczky, Gergö / Andersson, Anna-Lena / Sokolowski, Marcus

    Journal of safety research

    2022  Volume 83, Page(s) 232–237

    Abstract: Background: Suicides in the railway system is a serious health, societal, and transportation concern. Restriction of the access to suicide methods in the form of different physical barriers is a promising approach for suicide prevention.: Method: Mid- ...

    Abstract Background: Suicides in the railway system is a serious health, societal, and transportation concern. Restriction of the access to suicide methods in the form of different physical barriers is a promising approach for suicide prevention.
    Method: Mid-track fencing, which is fencing placed in-between the high-speed and commuter train tracks, was installed at one out of seven stations along a train line outside of Stockholm in the years 2013/2014. The number of suicides at the intervention station was compared to six other stations used as controls, over a total period of 20 years (2002-2021).
    Results: Suicides at high-speed tracks occurring at stations was the major cause of death on the investigated railway line. Prior to the year 2014, the intervention and control stations displayed similar time trends in the number of suicides. After installation of the mid-track fencing in 2014, there was a 62.5% reduction in the rate of suicides occurring at the intervention station. Compared to the six other control stations, the intervention station displayed a significant reduction in the number of suicides during the years 2014-2021 (OR = 0.14, 95%CI 0.013-0.95). Suicides at the railway lines in-between stations were not increased post-intervention. However, nearby control stations showed a 162% increase in suicides after the intervention, suggesting the induction of transfer effects.
    Conclusion: Mid-track fences restricting access to high-speed train tracks may have a large effect on reducing the number of railway suicides at intervention stations, but may also induce an increase in suicides at nearby stations without mid-track fences.
    Practical applications: Partial physical barriers such as mid-track fencing is deemed to be relatively easy and cheap to install (as compared to full barriers; e.g., full height platform screen doors) and should be considered at all stations on railway lines that have high-speed trains passing by.
    MeSH term(s) Humans ; Suicide ; Pilot Projects ; Suicide Prevention
    Language English
    Publishing date 2022-09-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2015321-1
    ISSN 1879-1247 ; 0022-4375
    ISSN (online) 1879-1247
    ISSN 0022-4375
    DOI 10.1016/j.jsr.2022.08.019
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  7. Article ; Online: Gene-level associations in suicide attempter families show overrepresentation of synaptic genes and genes differentially expressed in brain development.

    Sokolowski, Marcus / Wasserman, Jerzy / Wasserman, Danuta

    American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics

    2018  Volume 177, Issue 8, Page(s) 774–784

    Abstract: Suicidal behavior (SB) has a complex etiology involving different polygenic and environmental components. Here we used an excess of significant markers (ESM) test to study gene-level associations in previous genome-wide association studies (GWAS) SNP ... ...

    Abstract Suicidal behavior (SB) has a complex etiology involving different polygenic and environmental components. Here we used an excess of significant markers (ESM) test to study gene-level associations in previous genome-wide association studies (GWAS) SNP data from a family-based sample, having medically severe suicide attempt (SA) as main outcome in the offspring. In SA without major psychiatric disorders (N = 498), a screening of 5,316 genes across the genome suggested association 17 genes (at fdr < 0.05). Genes RETREG1 (a.k.a. FAM134B), GSN, GNAS, and CACNA1D were particularly robust to different methodological variations. Comparison with the more widely used Multi-marker Analysis of GenoMic Annotation (MAGMA) methods, mainly supported RETREG1, GSN, RNASEH2B, UBE2H, and CACNA1D by using the "mean" model, and ranked 13 of the same genes as ESM among its top-17. Complementing the ESM screen by using MAGMA to analyze 17,899 genes, we observed excess of genes with p < .05 by using the "top" model, and the "mean" model suggested additional genes with genome-wide fdr < 0.25. Overrepresentation analysis of 10 selected gene sets using all genes with p < .05, showed significant results for synaptic genes, genes differentially expressed in brain development and for ~12% of the SA polygenic association genes identified previously in this sample. Exploratory analysis linked some of the ESM top-17 genes to psychotropic drugs and we examined the allelic heterogeneity in the previous SA candidate GRIN2B. This study complemented previous GWAS on SB outcomes, implicating both previous candidate (e.g., GRIN2B and GNAS) and novel genes in SA outcomes, as well as synaptic functions and brain development.
    MeSH term(s) Adult ; Brain/embryology ; Brain/physiology ; Calcium Channels, L-Type/genetics ; Case-Control Studies ; Chromogranins/genetics ; Female ; GTP-Binding Protein alpha Subunits, Gs/genetics ; Genetic Markers/genetics ; Genetic Predisposition to Disease/genetics ; Genome-Wide Association Study/methods ; Genotype ; Humans ; Intracellular Signaling Peptides and Proteins ; Male ; Membrane Proteins ; Middle Aged ; Multifactorial Inheritance/genetics ; Neoplasm Proteins/genetics ; Polymorphism, Single Nucleotide/genetics ; Receptors, N-Methyl-D-Aspartate/genetics ; Risk Factors ; Suicidal Ideation ; Suicide/psychology ; Suicide, Attempted/psychology ; Synapses/genetics ; Transcriptome/genetics ; Ukraine
    Chemical Substances CACNA1D protein, human ; Calcium Channels, L-Type ; Chromogranins ; Genetic Markers ; Intracellular Signaling Peptides and Proteins ; Membrane Proteins ; NR2B NMDA receptor ; Neoplasm Proteins ; RETREG1 protein, human ; Receptors, N-Methyl-D-Aspartate ; GNAS protein, human (EC 3.6.1.-) ; GTP-Binding Protein alpha Subunits, Gs (EC 3.6.5.1)
    Language English
    Publishing date 2018-10-31
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2143866-3
    ISSN 1552-485X ; 1552-4841
    ISSN (online) 1552-485X
    ISSN 1552-4841
    DOI 10.1002/ajmg.b.32694
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  8. Article ; Online: Rare CNVs in Suicide Attempt include Schizophrenia-Associated Loci and Neurodevelopmental Genes: A Pilot Genome-Wide and Family-Based Study.

    Sokolowski, Marcus / Wasserman, Jerzy / Wasserman, Danuta

    PloS one

    2016  Volume 11, Issue 12, Page(s) e0168531

    Abstract: Suicidal behavior (SB) has a complex etiology involving genes and environment. One of the genetic components in SB could be copy number variations (CNVs), as CNVs are implicated in neurodevelopmental disorders. However, a recently published genome-wide ... ...

    Abstract Suicidal behavior (SB) has a complex etiology involving genes and environment. One of the genetic components in SB could be copy number variations (CNVs), as CNVs are implicated in neurodevelopmental disorders. However, a recently published genome-wide and case-control study did not observe any significant role of CNVs in SB. Here we complemented these initial observations by instead using a family-based trio-sample that is robust to control biases, having severe suicide attempt (SA) in offspring as main outcome (n = 660 trios). We first tested for CNV associations on the genome-wide Illumina 1M SNP-array by using FBAT-CNV methodology, which allows for evaluating CNVs without reliance on CNV calling algorithms, analogous to a common SNP-based GWAS. We observed association of certain T-cell receptor markers, but this likely reflected inter-individual variation in somatic rearrangements rather than association with SA outcome. Next, we used the PennCNV software to call 385 putative rare (<1%) and large (>100 kb) CNVs, observed in n = 225 SA offspring. Nine SA offspring had rare CNV calls in a set of previously schizophrenia-associated loci, indicating the importance of such CNVs in certain SA subjects. Several additional, very large (>1MB) sized CNV calls in 15 other SA offspring also spanned pathogenic regions or other neural genes of interest. Overall, 45 SA had CNVs enriched for 65 medically relevant genes previously shown to be affected by CNVs, which were characterized by a neurodevelopmental biology. A neurodevelopmental implication was partly congruent with our previous SNP-based GWAS, but follow-up analysis here indicated that carriers of rare CNVs had a decreased burden of common SNP risk-alleles compared to non-carriers. In conclusion, while CNVs did not show genome-wide association by the FBAT-CNV methodology, our preliminary observations indicate rare pathogenic CNVs affecting neurodevelopmental functions in a subset of SA, who were distinct from SA having increased SNP risk-allele burden. These observations may open up new avenues in the genetic etiology of SB.
    MeSH term(s) Adult ; Algorithms ; DNA Copy Number Variations/genetics ; Female ; Genome, Human ; Genome-Wide Association Study ; Genotype ; Humans ; Incidence ; Male ; Middle Aged ; Neurodevelopmental Disorders/genetics ; Neurodevelopmental Disorders/pathology ; Polymorphism, Single Nucleotide/genetics ; Risk Assessment ; Schizophrenia/genetics ; Schizophrenia/pathology ; Suicide, Attempted ; Young Adult
    Language English
    Publishing date 2016
    Publishing country United States
    Document type Journal Article
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0168531
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  9. Article ; Online: Polygenic risk scores for neuropsychiatric, inflammatory, and cardio-metabolic traits highlight possible genetic overlap with suicide attempt and treatment-emergent suicidal ideation.

    Fanelli, Giuseppe / Sokolowski, Marcus / Wasserman, Danuta / Kasper, Siegfried / Zohar, Joseph / Souery, Daniel / Montgomery, Stuart / Albani, Diego / Forloni, Gianluigi / Ferentinos, Panagiotis / Rujescu, Dan / Mendlewicz, Julien / De Ronchi, Diana / Serretti, Alessandro / Fabbri, Chiara

    American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics

    2022  Volume 189, Issue 3-4, Page(s) 74–85

    Abstract: Suicide is the second cause of death among youths. Genetics may contribute to suicidal phenotypes and their co-occurrence in other neuropsychiatric and medical conditions. Our study aimed to investigate the association of polygenic risk scores (PRSs) for ...

    Abstract Suicide is the second cause of death among youths. Genetics may contribute to suicidal phenotypes and their co-occurrence in other neuropsychiatric and medical conditions. Our study aimed to investigate the association of polygenic risk scores (PRSs) for 24 neuropsychiatric, inflammatory, and cardio-metabolic traits/diseases with suicide attempt (SA) or treatment-worsening/emergent suicidal ideation (TWESI). PRSs were computed based on summary statistics of genome-wide association studies. Regression analyses were performed between PRSs and SA or TWESI in four clinical cohorts. Results were then meta-analyzed across samples, including a total of 688 patients with SA (N
    MeSH term(s) Adolescent ; Coronary Artery Disease/genetics ; Depressive Disorder, Major/genetics ; Depressive Disorder, Major/psychology ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Phenotype ; Risk Factors ; Suicidal Ideation ; Suicide, Attempted/psychology
    Language English
    Publishing date 2022-02-21
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2108616-3
    ISSN 1552-485X ; 1552-4841 ; 0148-7299
    ISSN (online) 1552-485X
    ISSN 1552-4841 ; 0148-7299
    DOI 10.1002/ajmg.b.32891
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  10. Article ; Online: Genome-wide association studies of suicidal behaviors: a review.

    Sokolowski, Marcus / Wasserman, Jerzy / Wasserman, Danuta

    European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology

    2014  Volume 24, Issue 10, Page(s) 1567–1577

    Abstract: Suicidal behaviors represent a fatal dimension of mental ill-health, involving both environmental and heritable (genetic) influences. The putative genetic components of suicidal behaviors have until recent years been mainly investigated by hypothesis- ... ...

    Abstract Suicidal behaviors represent a fatal dimension of mental ill-health, involving both environmental and heritable (genetic) influences. The putative genetic components of suicidal behaviors have until recent years been mainly investigated by hypothesis-driven research (of "candidate genes"). But technological progress in genotyping has opened the possibilities towards (hypothesis-generating) genomic screens and novel opportunities to explore polygenetic perspectives, now spanning a wide array of possible analyses falling under the term Genome-Wide Association Study (GWAS). Here we introduce and discuss broadly some apparent limitations but also certain developing opportunities of GWAS. We summarize the results from all the eight GWAS conducted up to date focused on suicidality outcomes; treatment emergent suicidal ideation (3 studies), suicide attempts (4 studies) and completed suicides (1 study). Clearly, there are few (if any) genome-wide significant and reproducible findings yet to be demonstrated. We then discuss and pinpoint certain future considerations in relation to sample sizes, the units of genetic associations used, study designs and outcome definitions, psychiatric diagnoses or biological measures, as well as the use of genomic sequencing. We conclude that GWAS should have a lot more potential to show in the case of suicidal outcomes, than what has yet been realized.
    MeSH term(s) Genome-Wide Association Study/methods ; Humans ; Suicide
    Language English
    Publishing date 2014-10
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1082947-7
    ISSN 1873-7862 ; 0924-977X
    ISSN (online) 1873-7862
    ISSN 0924-977X
    DOI 10.1016/j.euroneuro.2014.08.006
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