Any disagreements were resolved via discussion and input from a third investigator. meeting or conference abstracts) were excluded. Studies that were conducted exclusively on animals, children under 16 years, not published in English, or where data was only published in abstract form (e.g. We included only GWASs of ADs, non-diagnostic traits (such as anxiety sensitivity), and neuroticism. Two investigators then independently screened the remaining full-text papers for eligible studies ( Figure 1). Next, abstracts not mentioning GWAS and either anxiety disorders, anxiety traits, or neuroticism, were removed. We merged our search results and removed any duplicates. Given the high comorbidity and genetic overlap between ADs and neuroticism, GWASs of neuroticism were included in this review. The following search query was used for PubMed and modified appropriately for other databases – no limits were used: ((genome-wide association study OR genome-wide association studies) OR (genome wide association study OR genome wide association studies) OR (GWAS OR GWA study OR GWA studies) OR ("Genome-Wide Association Study") OR (whole genome association study OR whole genome association studies OR genome wide association scan OR genome wide association scans OR genome wide association analysis OR genome wide association analyses)) AND ((anxiety disorder OR anxiety disorders) OR (anxiety neurosis OR anxiety neuroses OR anxiety neurotic) OR "Anxiety Disorders")). All databases were searched up to 2 June 2022. We also searched Web of Science and WorldCat for grey literature and hand-searched the reference lists of eligible studies for additional reports. We systematically searched PubMed, Scopus, PsychInfo and PubPsych. PRISMA guidelines were used to identify relevant studies for inclusion (Page et al. The study protocol for this review was registered with the international prospective register of systematic reviews (PROSPERO protocol CRD42021118062). Summarise SNP associations identified by GWASs of AD and neuroticism, combining results in a meta-analysis, if appropriate.Īppraise the quality of individual studies and assess the ancestral diversity of study participants. Recent articles raise concern over the persistent lack of ancestral diversity in GWAS, which limits the accuracy and broader relevance of findings, and threatens to exacerbate existing healthcare disparities as genomic medicine advances (Need and Goldstein Citation2009 Popejoy and Fullerton Citation2016 Peterson et al. GWAS, and more recently meta- and “mega” -analysis of GWAS (in which collaborative groups collate data for joint analysis) is a powerful method for detecting genetic associations for complex traits.Ī growing number of GWASs have examined anxiety and anxiety-related traits, such as neuroticism, but these have not been systematically summarised or meta-analysed. Genome-wide association studies (GWAS) test large numbers of SNPs for association with a given phenotype. This genetic contribution is complex, likely involving a large number of genes of a small individual effect, coupled with gene-gene and gene-environment interactions (Smoller et al. Citation2018)).ĪDs and neuroticism have a considerable genetic component, with a heritability of between 20 and 40%, (Smoller et al. Citation2020) with neuroticism possibly representing an “endophenotype” of ADs and other psychiatric disorders (similar evidence exists for the major depressive disorder) (Hettema et al. Neuroticism is highly comorbid with ADs clinically (Jylhä and Isometsä Citation2006), and there is a significant genetic correlation between the risk of ADs and neuroticism (previous studies suggest a genetic correlation of about 0.8) (Hettema et al. Neuroticism is one of the higher-order domains in the five-factor model of personality and represents individual differences in the tendency towards negative emotions or negative thoughts (Costa and Mccrae Citation1992 Goldberg Citation1993). These disorders are associated with significant distress and can culminate in serious disability. ADs are relatively common with a current prevalence of about 7.3% (Baxter et al. This group of disorders, which includes panic disorder (PD), social anxiety disorder, specific phobia and generalised anxiety disorder (GAD), may involve underlying dysregulation of the basic-threat response (Craske et al. Anxiety disorders (ADs) are a group of conditions characterised by excessive and enduring fear, anxiety or avoidance of perceived threats (Craske et al.
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