Genetic variants and susceptibility to severe COVID-19: a scoping review protocol (Preprint)

2021 ◽  
Author(s):  
Estephania Candelo ◽  
Juan David Gutiérrez-Medina ◽  
Andrés Gempeler ◽  
Lorena Diaz-Ordoñez ◽  
Harry Pachajoa
Keyword(s):  
Scoping Review ◽  
Genetic Variants ◽  
Association Studies ◽  
Library Science ◽  
Google Scholar ◽  
Cochrane Library ◽  
Genome Wide Association Studies ◽  
Gene Variants ◽  
Antibody Diversity ◽  
The Cochrane Library

BACKGROUND Coronavirus disease 19 (COVID-19), the disease caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is already responsible for more than four and a half million deaths worldwide. With a unique pathophysiology related to respiratory failure due to interstitial pneumonia and acute respiratory distress syndrome, severe COVID-19 is qualitatively different from moderate disease. Since genetics play a crucial role in susceptibility to viral infection and propensity to develop harmful inflammatory conditions, genetic heterogeneity promotes the question of whether gene variants might influence COVID-19 outcomes. The identification of genetic variants associated with severe courses of COVID-19 is a promising option for the improvement of prognostic tools, contemplation of new therapeutic targets and the development of patient’s clinical risk stratification. OBJECTIVE We aim to perform a scoping review to assess the extent of the literature regarding the gene variants that could be associated with COVID-19 severity. METHODS The proposed scoping review will be conducted in accordance with the methodology from the Joanna Briggs Institute’s Scoping Review Network.12 The search strategy will focus on published studies without discriminating in date or language. A multiple-database search (MEDLINE, LILACS, The Cochrane Library, Science Direct, Google Scholar and OpenGrey) will be done performing the following strategy: ((("COVID-19"[Mesh] OR "SARS-CoV-2"[Mesh]) AND ("Polymorphism, Genetic"[Mesh] OR "Mutation"[Mesh] OR "Antibody Diversity"[Mesh] OR "Antigenic Variation"[Mesh]) AND ("Severity of Illness Index"[Mesh] OR "Death"[Mesh] OR "Critical Care"[Mesh] OR "Critical Illness"[Mesh] OR (severity))). This scoping review will consider observational studies and genome-wide association studies (GWAS) without discriminating in date or language. Additionally, systematic reviews that meet the inclusion criteria will also be considered. Data will be extracted from papers included in the scoping review by two independent reviewers using an already existent data extraction tool. RESULTS The conducted search was performed on February 16th in MEDLINE, LILACS, The Cochrane Library, Science Direct, Google Scholar and OpenGrey retrieved a total of 2190 results. Completion of the review is expected in late 2021. CONCLUSIONS This scoping review will be the first to map the extent of information regarding the genetic variants associated to the severity of COVID-19. The data gathered by this investigation could lead to biomarkers of severity in COVID-19 and the stratification of patients according to their genetic risk of disease severity.

scholarly journals What Is the Heritability of Periodontitis? A Systematic Review

2019 ◽  
Vol 98 (6) ◽  
pp. 632-641 ◽  
Author(s):  
L. Nibali ◽  
J. Bayliss-Chapman ◽  
S.A. Almofareh ◽  
Y. Zhou ◽  
K. Divaris ◽  
...  
Keyword(s):  
Systematic Review ◽  
Disease Severity ◽  
Genetic Factors ◽  
Association Studies ◽  
Severe Disease ◽  
Family Studies ◽  
Google Scholar ◽  
Cochrane Library ◽  
Genome Wide Association Studies ◽  
Hand Search

The aim of this study was to systematically appraise the existing literature on the yet-unclear heritability of gingivitis and periodontitis. This review was conducted following the PRISMA guidelines. A search was conducted through the electronic databases Medline, Embase, LILACS, Cochrane Library, Open Grey, Google Scholar, and Research Gate, as complemented by a hand search, for human studies reporting measures of heritability of gingivitis and periodontitis. A total of 9,037 papers were initially identified from combined databases and 10,810 on Google Scholar. After full-text reading, 28 articles met the inclusion criteria and were carried forward to data abstraction. The reviewed data included information from >50,000 human subjects. Meta-analyses were performed by grouping studies based on design and outcome. Heritability ( H2) of periodontitis was estimated at 0.38 (95% CI, 0.34 to 0.43; I2 = 12.9%) in twin studies, 0.15 (95% CI, 0.06 to 0.24; I2 = 0%) in other family studies, and 0.29 (95% CI, 0.21 to 0.38; I2 = 61.2%) when twin and other family studies were combined. Genome-wide association studies detected a lower heritability estimate of 0.07 (95% CI, −0.02 to 0.15) for combined definitions of periodontitis, increasing with disease severity and when the interaction with smoking was included. Furthermore, heritability tended to be lower among older age groups. Heritability for the self-reported gingivitis trait was estimated at 0.29 (95% CI, 0.22 to 0.36; I2 = 37.6%), while it was not statistically significant for clinically measured gingivitis. This systematic review brings forward summary evidence to confirm that up to a third of the periodontitis variance in the population is due to genetic factors. This seems consistent across the different studied populations and increases with disease severity. In summary, up to a third of the variance of periodontitis in the population is due to genetic factors, with higher heritability for more severe disease.

Migraine: Genetic Variants and Clinical Phenotypes

2019 ◽  
Vol 26 (34) ◽  
pp. 6207-6221 ◽  
Author(s):  
Innocenzo Rainero ◽  
Alessandro Vacca ◽  
Flora Govone ◽  
Annalisa Gai ◽  
Lorenzo Pinessi ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Association Studies ◽  
Mthfr Gene ◽  
Genome Wide Association Studies ◽  
Clinical Phenotypes ◽  
Network Analyses ◽  
Genome Wide ◽  
Genomic Studies ◽  
The Common ◽  
The Relationship

Migraine is a common, chronic neurovascular disorder caused by a complex interaction between genetic and environmental risk factors. In the last two decades, molecular genetics of migraine have been intensively investigated. In a few cases, migraine is transmitted as a monogenic disorder, and the disease phenotype cosegregates with mutations in different genes like CACNA1A, ATP1A2, SCN1A, KCNK18, and NOTCH3. In the common forms of migraine, candidate genes as well as genome-wide association studies have shown that a large number of genetic variants may increase the risk of developing migraine. At present, few studies investigated the genotype-phenotype correlation in patients with migraine. The purpose of this review was to discuss recent studies investigating the relationship between different genetic variants and the clinical characteristics of migraine. Analysis of genotype-phenotype correlations in migraineurs is complicated by several confounding factors and, to date, only polymorphisms of the MTHFR gene have been shown to have an effect on migraine phenotype. Additional genomic studies and network analyses are needed to clarify the complex pathways underlying migraine and its clinical phenotypes.

scholarly journals Case–Parent Trio Studies in Cleft Lip and Palate

2020 ◽  
Vol 07 (03) ◽  
pp. 075-079
Author(s):  
Mahamad Irfanulla Khan ◽  
Prashanth CS
Keyword(s):  
Genetic Variants ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Association Studies ◽  
Geographical Location ◽  
Genetic Association Studies ◽  
Population Based ◽  
Genome Wide Association Studies ◽  
Family Based ◽  
Study Designs

AbstractCleft lip with or without cleft palate (CL/P) is one of the most common congenital malformations in humans involving various genetic and environmental risk factors. The prevalence of CL/P varies according to geographical location, ethnicity, race, gender, and socioeconomic status, affecting approximately 1 in 800 live births worldwide. Genetic studies aim to understand the mechanisms contributory to a phenotype by measuring the association between genetic variants and also between genetic variants and phenotype population. Genome-wide association studies are standard tools used to discover genetic loci related to a trait of interest. Genetic association studies are generally divided into two main design types: population-based studies and family-based studies. The epidemiological population-based studies comprise unrelated individuals that directly compare the frequency of genetic variants between (usually independent) cases and controls. The alternative to population-based studies (case–control designs) includes various family-based study designs that comprise related individuals. An example of such a study is a case–parent trio design study, which is commonly employed in genetics to identify the variants underlying complex human disease where transmission of alleles from parents to offspring is studied. This article describes the fundamentals of case–parent trio study, trio design and its significances, statistical methods, and limitations of the trio studies.

scholarly journals Editing GWAS: experimental approaches to dissect and exploit disease-associated genetic variation

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Shuquan Rao ◽  
Yao Yao ◽  
Daniel E. Bauer
Keyword(s):  
Genome Editing ◽  
Genetic Variants ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Functional Studies ◽  
Functional Genetics ◽  
Genome Wide ◽  
Causal Variants ◽  
Experimental Approaches

AbstractGenome-wide association studies (GWAS) have uncovered thousands of genetic variants that influence risk for human diseases and traits. Yet understanding the mechanisms by which these genetic variants, mainly noncoding, have an impact on associated diseases and traits remains a significant hurdle. In this review, we discuss emerging experimental approaches that are being applied for functional studies of causal variants and translational advances from GWAS findings to disease prevention and treatment. We highlight the use of genome editing technologies in GWAS functional studies to modify genomic sequences, with proof-of-principle examples. We discuss the challenges in interrogating causal variants, points for consideration in experimental design and interpretation of GWAS locus mechanisms, and the potential for novel therapeutic opportunities. With the accumulation of knowledge of functional genetics, therapeutic genome editing based on GWAS discoveries will become increasingly feasible.

scholarly journals Addressing barriers to the conduct and application of research in complementary and alternative medicine: a scoping review

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yasamin Veziari ◽  
Saravana Kumar ◽  
Matthew Leach
Keyword(s):  
Alternative Medicine ◽  
Complementary And Alternative Medicine ◽  
Scoping Review ◽  
Data Extraction ◽  
Grey Literature ◽  
Evidence Base ◽  
Cochrane Library ◽  
Educational Strategies ◽  
The Cochrane Library ◽  
Complementary And Alternative

Abstract Background Over the past few decades, the popularity of complementary and alternative medicine (CAM) has grown considerably and along with it, scrutiny regarding its evidence base. While this is to be expected, and is in line with other health disciplines, research in CAM is confronted by numerous obstacles. This scoping review aims to identify and report the strategies implemented to address barriers to the conduct and application of research in CAM. Methods The scoping review was undertaken using the Arksey and O’Malley framework. The search was conducted using MEDLINE, EMBASE, EMCARE, ERIC, Scopus, Web of Science, The Cochrane Library, JBI and the grey literature. Two reviewers independently screened the records, following which data extraction was completed for the included studies. Descriptive synthesis was used to summarise the data. Results Of the 7945 records identified, 15 studies met the inclusion criteria. Using the oBSTACLES instrument as a framework, the included studies reported diverse strategies to address barriers to the conduct and application of research in CAM. All included studies reported the use of educational strategies and collaborative initiatives with CAM stakeholders, including targeted funding, to address a range of barriers. Conclusions While the importance of addressing barriers to the conduct and application of research in CAM has been recognised, to date, much of the focus has been limited to initiatives originating from a handful of jurisdictions, for a small group of CAM disciplines, and addressing few barriers. Myriad barriers continue to persist, which will require concerted effort and collaboration across a range of CAM stakeholders and across multiple sectors. Further research can contribute to the evidence base on how best to address these barriers to promote the conduct and application of research in CAM.

scholarly journals Bias in two-sample Mendelian randomization when using heritable covariable-adjusted summary associations

2021 ◽  
Author(s):  
Fernando Pires Hartwig ◽  
Kate Tilling ◽  
George Davey Smith ◽  
Deborah A Lawlor ◽  
Maria Carolina Borges
Keyword(s):  
Waist Circumference ◽  
Genetic Variants ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Association Studies ◽  
Real Data ◽  
Sensitivity Analyses ◽  
Effect Estimate ◽  
Genome Wide Association Studies ◽  
Residual Confounding

Abstract Background Two-sample Mendelian randomization (MR) allows the use of freely accessible summary association results from genome-wide association studies (GWAS) to estimate causal effects of modifiable exposures on outcomes. Some GWAS adjust for heritable covariables in an attempt to estimate direct effects of genetic variants on the trait of interest. One, both or neither of the exposure GWAS and outcome GWAS may have been adjusted for covariables. Methods We performed a simulation study comprising different scenarios that could motivate covariable adjustment in a GWAS and analysed real data to assess the influence of using covariable-adjusted summary association results in two-sample MR. Results In the absence of residual confounding between exposure and covariable, between exposure and outcome, and between covariable and outcome, using covariable-adjusted summary associations for two-sample MR eliminated bias due to horizontal pleiotropy. However, covariable adjustment led to bias in the presence of residual confounding (especially between the covariable and the outcome), even in the absence of horizontal pleiotropy (when the genetic variants would be valid instruments without covariable adjustment). In an analysis using real data from the Genetic Investigation of ANthropometric Traits (GIANT) consortium and UK Biobank, the causal effect estimate of waist circumference on blood pressure changed direction upon adjustment of waist circumference for body mass index. Conclusions Our findings indicate that using covariable-adjusted summary associations in MR should generally be avoided. When that is not possible, careful consideration of the causal relationships underlying the data (including potentially unmeasured confounders) is required to direct sensitivity analyses and interpret results with appropriate caution.

scholarly journals Relative infectiousness of asymptomatic SARS-CoV-2 infected persons compared with symptomatic individuals: a rapid scoping review

BMJ Open ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. e042354
Author(s):  
David McEvoy ◽  
Conor McAloon ◽  
Aine Collins ◽  
Kevin Hunt ◽  
Francis Butler ◽  
...  
Keyword(s):  
Scoping Review ◽  
Quantitative Measure ◽  
Contact Tracing ◽  
Cochrane Library ◽  
International Studies ◽  
Screening Process ◽  
Modelling Studies ◽  
Asymptomatic Individuals ◽  
Definition Of ◽  
The Cochrane Library

ObjectivesThe aim of this study was to determine the relative infectiousness of asymptomatic SARS-CoV-2 infected persons compared with symptomatic individuals based on a scoping review of available literature.DesignRapid scoping review of peer-reviewed literature from 1 January to 5 December 2020 using the LitCovid database and the Cochrane library.SettingInternational studies on the infectiousness of individuals infected with SARS-CoV-2.ParticipantsStudies were selected for inclusion if they defined asymptomatics as a separate cohort distinct from presymptomatics and if they provided a quantitative measure of the infectiousness of asymptomatics relative to symptomatics.Primary outcome measuresPCR result (PCR studies), the rate of infection (mathematical modelling studies) and secondary attack rate (contact tracing studies) - in each case from asymptomatic in comparison with symptomatic individuals.ResultsThere are only a limited number of published studies that report estimates of relative infectiousness of asymptomatic compared with symptomatic individuals. 12 studies were included after the screening process. Significant differences exist in the definition of infectiousness. PCR studies in general show no difference in shedding levels between symptomatic and asymptomatic individuals; however, the number of study subjects is generally limited. Two modelling studies estimate relative infectiousness to be 0.43 and 0.57, but both of these were more reflective of the infectiousness of undocumented rather than asymptomatic cases. The results from contact tracing studies include estimates of relative infectiousness of 0, but with insufficient evidence to conclude that it is significantly different from 1.ConclusionsThere is considerable heterogeneity in estimates of relative infectiousness highlighting the need for further investigation of this important parameter. It is not possible to provide any conclusive estimate of relative infectiousness, as the estimates from the reviewed studies varied between 0 and 1.

scholarly journals CAUSALdb: a database for disease/trait causal variants identified using summary statistics of genome-wide association studies

2019 ◽  
Author(s):  
Jianhua Wang ◽  
Dandan Huang ◽  
Yao Zhou ◽  
Hongcheng Yao ◽  
Huanhuan Liu ◽  
...  
Keyword(s):  
Fine Mapping ◽  
Genetic Variants ◽  
Association Studies ◽  
Complex Trait ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Summary Statistics ◽  
Genome Wide ◽  
Credible Sets ◽  
Causal Variants

Abstract Genome-wide association studies (GWASs) have revolutionized the field of complex trait genetics over the past decade, yet for most of the significant genotype-phenotype associations the true causal variants remain unknown. Identifying and interpreting how causal genetic variants confer disease susceptibility is still a big challenge. Herein we introduce a new database, CAUSALdb, to integrate the most comprehensive GWAS summary statistics to date and identify credible sets of potential causal variants using uniformly processed fine-mapping. The database has six major features: it (i) curates 3052 high-quality, fine-mappable GWAS summary statistics across five human super-populations and 2629 unique traits; (ii) estimates causal probabilities of all genetic variants in GWAS significant loci using three state-of-the-art fine-mapping tools; (iii) maps the reported traits to a powerful ontology MeSH, making it simple for users to browse studies on the trait tree; (iv) incorporates highly interactive Manhattan and LocusZoom-like plots to allow visualization of credible sets in a single web page more efficiently; (v) enables online comparison of causal relations on variant-, gene- and trait-levels among studies with different sample sizes or populations and (vi) offers comprehensive variant annotations by integrating massive base-wise and allele-specific functional annotations. CAUSALdb is freely available at http://mulinlab.org/causaldb.

scholarly journals Scoping review protocol: the use of telemedicine in providing opioid agonist treatment and related psychosocial supports

BMJ Open ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. e040556
Author(s):  
Des Crowley ◽  
Robyn Homeniuk ◽  
Ide Delargy
Keyword(s):  
Scoping Review ◽  
Psychosocial Support ◽  
Descriptive Analysis ◽  
Cochrane Library ◽  
Opioid Use ◽  
Opioid Agonist ◽  
Opioid Agonist Treatment ◽  
Search Terms ◽  
Medical Librarian ◽  
The Cochrane Library

IntroductionThe global opioid-related disease burden is significant. Opioid agonist treatment (OAT) can be effective in reducing illicit opioid use and fatal overdose, and improving multiple health and social outcomes. Despite evidence for its effectiveness, there are significant deficits in OAT globally. COVID-19 has required rapid adaptation of remote models of healthcare. Telemedicine is not used routinely in OAT, and little is known about the current levels of use and effectiveness. The objective of this review is to describe models of telemedicine and their efficacy.Methods and analysisThis scoping review uses the review methodology described by Arksey and O’Malley and adapted by Levac et al. The search strategy developed by the medical librarian at the Irish College of General Practitioners in conjunction with the research team will involve five databases (PubMed, EMBASE, the Cochrane Library, PsycInfo and OpenGrey) and the hand searching of reference lists. A limited initial search of two databases will be completed to refine search terms, followed by a second comprehensive search using newly refined search terms of all databases and finally hand searching references of included studies. To be included, studies must report on remote ways of providing OAT (including assessment, induction and monitoring) or related psychosocial support; be published in English after 2010. Two researchers will independently screen titles, abstracts and full-text articles considered for inclusion. Data will be extracted onto an agreed template and will undergo a descriptive analysis of the contextual or process-oriented data and simple quantitative analysis using descriptive statistics.Ethics and disseminationResearch ethics approval is not required for this scoping review. The results of this scoping review will inform the development of a national remote model of OAT. The results will be published in peer-reviewed journals and presented at relevant conferences.

scholarly journals A Novel Method for Mendelian Randomization Analyses With Pleiotropy and Linkage Disequilibrium in Genetic Variants From Individual Data

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuquan Wang ◽  
Tingting Li ◽  
Liwan Fu ◽  
Siqian Yang ◽  
Yue-Qing Hu
Keyword(s):  
Linkage Disequilibrium ◽  
Genetic Variants ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Association Studies ◽  
Random Effect ◽  
Pleiotropic Effect ◽  
Genome Wide Association Studies ◽  
The Novel ◽  
Novel Method

Mendelian randomization makes use of genetic variants as instrumental variables to eliminate the influence induced by unknown confounders on causal estimation in epidemiology studies. However, with the soaring genetic variants identified in genome-wide association studies, the pleiotropy, and linkage disequilibrium in genetic variants are unavoidable and may produce severe bias in causal inference. In this study, by modeling the pleiotropic effect as a normally distributed random effect, we propose a novel mixed-effects regression model-based method PLDMR, pleiotropy and linkage disequilibrium adaptive Mendelian randomization, which takes linkage disequilibrium into account and also corrects for the pleiotropic effect in causal effect estimation and statistical inference. We conduct voluminous simulation studies to evaluate the performance of the proposed and existing methods. Simulation results illustrate the validity and advantage of the novel method, especially in the case of linkage disequilibrium and directional pleiotropic effects, compared with other methods. In addition, by applying this novel method to the data on Atherosclerosis Risk in Communications Study, we conclude that body mass index has a significant causal effect on and thus might be a potential risk factor of systolic blood pressure. The novel method is implemented in R and the corresponding R code is provided for free download.

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