Genetic sensitivity analysis: Adjusting for genetic confounding in epidemiological associations.
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ABSTRACT:
SUBMITTER: Pingault JB
PROVIDER: S-EPMC8238188 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundPrevious studies have showed that single nucleotide polymorphisms (SNPs) might be implicated in the pathogenesis of osteosarcoma (OS). Numerous studies involving SNPs with OS risk have been reported; these results, however, remain controversial and no comprehensive research synopsis has been performed till now.ObjectiveThis study seeks to clarify the relationships between SNPs and OS risk using a comprehensive meta-analysis, and assess epidemiological evidence of significant associations.MethodsThe PubMed, Web of Science, and Medline were used to screen for articles that evaluated the association between SNP and OS susceptibility in humans before 24 December 2021. Furthermore, we used Venice Criteria and a false positive report probability (FPRP) test to assess the grades of epidemiological evidence for the statistical relationships.ResultsWe extracted useful data based on 43 articles, including 10,255 cases and 13,733 controls. Our results presented that 25 SNPs in 17 genes were significantly associated with OS risk. Finally, we graded strong evidence for 17 SNPs in 14 genes with OS risk (APE1 rs1760944, BCAS1 rs3787547, CTLA4 rs231775, ERCC3 rs4150506, HOTAIR rs7958904, IL6 rs1800795, IL8 rs4073, MTAP rs7023329 and rs7027989, PRKCG rs454006, RECQL5 rs820196, TP53 rs1042522, VEGF rs3025039, rs699947 and rs2010963, VMP1 rs1295925, XRCC3 rs861539), moderate for 14 SNPs in 12 genes and weak for 14 SNPs in 11 genes.ConclusionIn summary, this study offered a comprehensive meta-analysis between SNPs and OS susceptibility, then evaluated the credibility of statistical relationships, and provided useful information to identify the appropriate candidate SNPs and design future studies to evaluate SNP factors for OS risk.
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Project description:Operations researchers worldwide rely extensively on quantitative simulations to model alternative aspects of the COVID-19 pandemic. Proper uncertainty quantification and sensitivity analysis are fundamental to enrich the modeling process and communicate correctly informed insights to decision-makers. We develop a methodology to obtain insights on key uncertainty drivers, trend analysis and interaction quantification through an innovative combination of probabilistic sensitivity techniques and machine learning tools. We illustrate the approach by applying it to a representative of the family of susceptible-infectious-recovered (SIR) models recently used in the context of the COVID-19 pandemic. We focus on data of the early pandemic progression in Italy and the United States (the U.S.). We perform the analysis for both cases of correlated and uncorrelated inputs. Results show that quarantine rate and intervention time are the key uncertainty drivers, have opposite effects on the number of total infected individuals and are involved in the most relevant interactions.
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Project description:BACKGROUND:Mediation analysis is a powerful tool for understanding mechanisms, but conclusions about direct and indirect effects will be invalid if there is unmeasured confounding of the mediator-outcome relationship. Sensitivity analysis methods allow researchers to assess the extent of this bias but are not always used. One particularly straightforward technique that requires minimal assumptions is nonetheless difficult to interpret, and so would benefit from a more intuitive parameterization. METHODS:We conducted an exhaustive numerical search over simulated mediation effects, calculating the proportion of scenarios in which a bound for unmeasured mediator-outcome confounding held under an alternative parameterization. RESULTS:In over 99% of cases, the bound for the bias held when we described the strength of confounding directly via the confounder-mediator relationship instead of via the conditional exposure-confounder relationship. CONCLUSIONS:Researchers can conduct sensitivity analysis using a method that describes the strength of the confounder-outcome relationship and the approximate strength of the confounder-mediator relationship that, together, would be required to explain away a direct or indirect effect.
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Project description:Despite the fact that randomization is the gold standard for estimating causal relationships, many questions in prevention science are often left to be answered through nonexperimental studies because randomization is either infeasible or unethical. While methods such as propensity score matching can adjust for observed confounding, unobserved confounding is the Achilles heel of most nonexperimental studies. This paper describes and illustrates seven sensitivity analysis techniques that assess the sensitivity of study results to an unobserved confounder. These methods were categorized into two groups to reflect differences in their conceptualization of sensitivity analysis, as well as their targets of interest. As a motivating example, we examine the sensitivity of the association between maternal suicide and offspring's risk for suicide attempt hospitalization. While inferences differed slightly depending on the type of sensitivity analysis conducted, overall, the association between maternal suicide and offspring's hospitalization for suicide attempt was found to be relatively robust to an unobserved confounder. The ease of implementation and the insight these analyses provide underscores sensitivity analysis techniques as an important tool for nonexperimental studies. The implementation of sensitivity analysis can help increase confidence in results from nonexperimental studies and better inform prevention researchers and policy makers regarding potential intervention targets.
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