FINDbase: a worldwide database for genetic variation allele frequencies updated

Frequency of INherited Disorders database (FIND base; http://www.findbase.org) records frequencies of causative genetic variations worldwide. Database records include the population and ethnic group or geographical region, the disorder name and the related gene, accompanied by links to any related external resources and the genetic variation together with its frequency in that population. In addition to the regular data content updates, we report the following significant advances: (i) the systematic collection and thorough documentation of population/ethnic group-specific pharmacogenomic markers allele frequencies for 144 markers in 14 genes of pharmacogenomic interest from different classes of drug-metabolizing enzymes and transporters, representing 150 populations and ethnic groups worldwide; (ii) the development of new data querying and visualization tools in the expanded FINDbase data collection, built around Microsoft’s PivotViewer software (http://www.getpivot.com), based on Microsoft Silverlight technology (http://www.silverlight.net) that facilitates querying of large data sets and visualizing the results; and (iii) the establishment of the first database journal, by affiliating FINDbase with Human Genomics and Proteomics, a new open-access scientific journal, which would serve as a prime example of a non-profit model for sustainable database funding

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Evidence from the Piraeus coastal plain and Elefsis bay sedimentary y records. Water

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Impacts of dietary exposure to pesticides on faecal microbiome metabolism in adult twins

BACKGROUND: Dietary habits have a profound influence on the metabolic activity of gut microorganisms and their influence on health. Concerns have been raised as to whether the consumption of foodstuffs contaminated with pesticides can contribute to the development of chronic disease by affecting the gut microbiome. We performed the first pesticide biomonitoring survey of the British population, and subsequently used the results to perform the first pesticide association study on gut microbiome composition and function from the TwinsUK registry. METHODS: Dietary exposure of 186 common insecticide, herbicide, or fungicide residues and the faecal microbiome in 65 twin pairs in the UK was investigated. We evaluated if dietary habits, geographic location, or the rural/urban environment, are associated with the excretion of pesticide residues. The composition and metabolic activity of faecal microbiota was evaluated using shotgun metagenomics and metabolomics respectively. We performed a targeted urine metabolomics analysis in order to evaluate whether pesticide urinary excretion was also associated with physiological changes. RESULTS: Pyrethroid and/or organophosphorus insecticide residues were found in all urine samples, while the herbicide glyphosate was found in 53% of individuals. Food frequency questionnaires showed that residues from organophosphates were higher with increased consumption of fruit and vegetables. A total of 34 associations between pesticide residue concentrations and faecal metabolite concentrations were detected. Glyphosate excretion was positively associated with an overall increased bacterial species richness, as well as to fatty acid metabolites and phosphate levels. The insecticide metabolite Br2CA, reflecting deltamethrin exposure, was positively associated with the phytoestrogens enterodiol and enterolactone, and negatively associated with some N-methyl amino acids. Urine metabolomics performed on a subset of samples did not reveal associations with the excretion of pesticide residues. CONCLUSIONS: The consumption of conventionally grown fruit and vegetables leads to higher ingestion of pesticides with unknown long-term health consequences. Our results highlight the need for future dietary intervention studies to understand effects of pesticide exposure on the gut microbiome and possible health consequences. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12940-022-00860-0

UEG and EAES rapid guideline: Update systematic review, network meta-analysis, CINeMA and GRADE assessment, and evidence-informed European recommendations on surgical management of GERD

Background: There are several options for the surgical management of GERD in adults. Previous guidelines and systematic reviews have compared the effects of total fundoplication versus pooled effects of different techniques of partial fundoplication. Objective: To develop evidence-informed, trustworthy, pertinent recommendations on the use of total, posterior partial and anterior partial fundoplications for the management of GERD in adults. Methods: We performed an update systematic review, network meta-analysis, and evidence appraisal using the GRADE and the Confidence in Network Meta-Analysis methodologies. An international, multidisciplinary panel of surgeons, gastroenterologists, and a patient representative reached unanimous consensus through an evidence-to-decision framework to select among multiple interventions, and a Delphi process to formulate the recommendation. The project was developed in an online authoring and publication platform (MAGICapp), and was overseen by an external auditor. Results: We suggest posterior partial fundoplication over total posterior or anterior 90° fundoplication in adult patients with GERD. We suggest anterior >90° fundoplication as an alternative, although relevant comparative evidence is limited (weak recommendation). The guideline, with recommendations, evidence summaries and decision aids in user friendly formats can also be accessed in MAGICapp: https://app.magicapp.org/#/guideline/j20X4n. Conclusion: This rapid guideline was developed in line with highest methodological standards and provides evidence-informed recommendations on the surgical management of GERD. It provides user-friendly decision aids to inform healthcare professionals' and patients' decision making

UEG and EAES rapid guideline: Update systematic review, network meta-analysis, CINeMA and GRADE assessment, and evidence-informed European recommendations on surgical management of GERD.

BACKGROUND: There are several options for the surgical management of GERD in adults. Previous guidelines and systematic reviews have compared the effects of total fundoplication versus pooled effects of different techniques of partial fundoplication. OBJECTIVE: To develop evidence-informed, trustworthy, pertinent recommendations on the use of total, posterior partial and anterior partial fundoplications for the management of GERD in adults. METHODS: We performed an update systematic review, network meta-analysis, and evidence appraisal using the GRADE and the Confidence in Network Meta-Analysis methodologies. An international, multidisciplinary panel of surgeons, gastroenterologists, and a patient representative reached unanimous consensus through an evidence-to-decision framework to select among multiple interventions, and a Delphi process to formulate the recommendation. The project was developed in an online authoring and publication platform (MAGICapp), and was overseen by an external auditor. RESULTS: We suggest posterior partial fundoplication over total posterior or anterior 90° fundoplication in adult patients with GERD. We suggest anterior >90° fundoplication as an alternative, although relevant comparative evidence is limited (weak recommendation). The guideline, with recommendations, evidence summaries and decision aids in user friendly formats can also be accessed in MAGICapp: https://app.magicapp.org/#/guideline/j20X4n. CONCLUSION: This rapid guideline was developed in line with highest methodological standards and provides evidence-informed recommendations on the surgical management of GERD. It provides user-friendly decision aids to inform healthcare professionals' and patients' decision making