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    SchizophreniaGene (SZGene) database

    Category  Cross-Omics>Knowledge Bases/Databases/Tools

    Abstract  The SchizophreniaGene (SZGene) database aims to provide
    a comprehensive, unbiased and regularly updated collection of 'genetic
    association studies' performed on schizophrenia phenotypes.

    Eligible publications are identified following systematic searches of
    scientific literature databases, as well as the table of contents of
    journals in genetics and psychiatry.

    The database can be searched either by a variety of dropdown menus
    or by specific keywords. For each gene, summary overviews are
    provided displaying key characteristics for each publication, including
    links to genotype distributions of the polymorphisms studied, random-
    effects allelic meta-analyses, and funnel plots for an assessment of
    publication bias.

    Database Organization and Methods --

    If an association study also included subjects afflicted with disorders
    other than schizophrenia (e.g., bipolar disorder or schizoaffective
    disorder), generally only samples fulfilling diagnostic criteria for
    schizophrenia are included in the database and subsequent analyses,
    if they were listed separately in the original publication.

    Data selected for display summarize key characteristics of the
    investigated study cohorts (e.g., gene overview), as well as genotype
    distributions in cases and controls (e.g., polymorphism details).

    For polymorphisms with genotype data in at least four (4) case-control
    samples, continuously updated random-effects meta-analyses are
    presented (see meta-analysis methods below...).

    Note that data obtained from family-based studies are Not included in
    the meta-analyses, as crude odds ratios cannot be readily calculated
    from overall genotype distributions.

    However, these studies and their qualitative results are still listed on the
    ‘gene-summary’ pages of the SZGene website.

    Meta-Analysis Methods --

    For all polymorphisms with minor allele frequencies in healthy controls
    >1%, and for which case-control genotype data are available in four (4)
    or more independent samples, crude odds ratios (ORs) and 95 percent
    confidence intervals (CIs) are calculated from the reported allele
    distributions for each study.

    Summary ORs and 95 percent CIs are calculated using the
    DerSimonian and Laird (1986) random-effects model, which utilizes
    weights that incorporate both within-study and between-study variance.

    This procedure is done including all studies irrespective of ethnicity
    (denoted by "All Studies" on the meta-analysis figures), and repeated
    after exclusion of the initial study ("All Excl Initial Study"), after exclusion
    of studies in which a deviation of Hardy-Weinberg Equilibrium (HWE)
    was detected in controls ("All Excl HWE Deviations"), and after exclusion
    of samples of non-Caucasian ancestry ("All Caucasian Studies").

    Overlapping samples (of which usually only the largest is included),
    studies with missing data, or control samples deviating from HWE are
    indicated on the meta-analysis graphs.

    Please note, that when only a few studies are included in the meta-
    analyses (i.e. less than ~10), the random effects model may yield
    summary ORs and confidence bounds that are slightly anti-conservative.

    To allow a visual assessment of the presence of publication bias (or
    other sorts of reporting bias), the manufacturer uses a Begg modified
    funnel plot which depicts the allele-specific OR (on a logarithmic scale)
    against its standard error for each study (Egger, 1997) including studies
    of all ethnicities.

    Note that the power to detect deviations from a symmetrical distribution
    is limited, especially for analyses based on less than ~20 individual
    studies.

    Inclusion of Genome-wide Association (GWA) Analyses --

    The manufacturer has devised the following step-wise protocol, which
    they believe allows them to capture the most relevant genetic
    information without the need to include every data-point from these
    studies.

    Note that this feature of SZGene is new and still under development.

    Please visit the "Overview of all published large-scale and genome-
    wide association studies in SZ" page to see a summary of all published
    large-scale studies currently included in SZGene.

    SZGene Stage 1 - Represents the inclusion of genes and
    polymorphisms “featured” or highlighted by the authors of the large-
    scale study, usually because they show some degree of genetic
    association after completion of all analyses, e.g. testing multiple
    independent samples.

    These genes and polymorphisms probably represent the most
    important findings of each large-scale analysis and are therefore
    included here with highest priority.

    This stage has already been implemented in the current version of
    SZGene (e.g. for the CSF2RA gene featured in the GWA study by Lencz
    et al. [2007]).

    For large-scale/GWA studies that have made their genotype data
    publicly available, the manufacturer will also make use of “non-featured”
    genotype distributions, i.e. of polymorphisms Not believed to be
    associated with schizophrenia in the original publications:

    SZGene Stage 2 - Will add large-scale/GWA genotype data for
    polymorphisms already available in SZGene, i.e. usually derived from
    candidate gene studies published prior to 2007.

    Large-scale/GWA data for such overlapping polymorphisms will be
    added to the gene-specific entries and, if genotype data is then
    available in a total of at least four (4) independent case-control
    samples, included and displayed in the meta-analyses.

    This stage adds valuable information to the existing SZGene meta-
    analyses as it is derived from assessments that are largely unbiased
    with respect to gene function, in contrast to most conventional candidate
    gene studies. This feature is Not yet available in SZGene.

    SZGene Stage 3 - Applies to GWA studies only. If genotype distributions
    are publicly available for multiple GWA scans, the manufacturer will
    perform systematic meta-analyses for all markers overlapping in at
    least four (4) independent case-control samples. Only those showing
    significant summary ORs will be displayed on the SZGene website.

    The threshold of declaring statistical significance (resulting in being
    displayed at the front-end of the database) in this context will be more
    stringent, due to the large number of tests performed (i.e. P-values of
    the summary ORs <<0.05).

    Procedures for implementing this stage and the definition of
    appropriate threshold criteria is currently underway and will follow
    guidelines suggested previously (Evangelou, 2007). This feature is Not
    yet available in SZGene.

    Summary of Meta-analysis Highlights: The "Top Results" List --

    In an effort to facilitate the identification of the most promising meta-
    analysis results available in SZGene, a continuously updated list
    displaying the most strongly associated genes ("Top Results") has
    been added to the manufacturer's homepage.

    The list is ranked by effect size, and only includes genes that contain at
    least one variant showing a nominally significant summary OR in the
    analysis of all ethnic groups (“All”), or those limited to samples of
    Caucasian ancestry (“Caucasian only”).

    While the manufacturer believes that this list represents an up-to-date
    summary of particularly promising schizophrenia candidate genes that
    warrant follow-up with high priority, the manufacturer notes that many of
    these may represent false-positive findings, in particular those based
    on small (<10) sample sizes.

    System Requirements  

    Web based

    Manufacturer   
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