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Gene-environment correlation: difficulties and a natural experiment-based strategy.

ABSTRACT: We explored how gene-environment correlations can result in endogenous models, how natural experiments can protect against this threat, and if unbiased estimates from natural experiments are generalizable to other contexts.We compared a natural experiment, the College Roommate Study, which measured genes and behaviors of college students and their randomly assigned roommates in a southern public university, with observational data from the National Longitudinal Study of Adolescent Health in 2008. We predicted exposure to exercising peers using genetic markers and estimated environmental effects on alcohol consumption. A mixed-linear model estimated an alcohol consumption variance that was attributable to genetic markers and across peer environments.Peer exercise environment was associated with respondent genotype in observational data, but not in the natural experiment. The effects of peer drinking and presence of a general gene-environment interaction were similar between data sets.Natural experiments, like random roommate assignment, could protect against potential bias introduced by gene-environment correlations. When combined with representative observational data, unbiased and generalizable causal effects could be estimated.

SUBMITTER: Wagner B

PROVIDER: S-EPMC3778033 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Gene-environment correlation: difficulties and a natural experiment-based strategy.

Wagner Brandon B Li Jiang J Liu Hexuan H Guo Guang G

American journal of public health 20130808

<h4>Objectives</h4>We explored how gene-environment correlations can result in endogenous models, how natural experiments can protect against this threat, and if unbiased estimates from natural experiments are generalizable to other contexts.<h4>Methods</h4>We compared a natural experiment, the College Roommate Study, which measured genes and behaviors of college students and their randomly assigned roommates in a southern public university, with observational data from the National Longitudinal ...[more]

PMID: 23927502

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Project description:BackgroundIn a health care system based on managed competition it is important that health insurers are able to channel their enrolees to preferred care providers. However, enrolees are often very negative about financial incentives and any limitations in their choice of care provider. Therefore, a Dutch health insurance company conducted an experiment to study the effectiveness of a new method of channelling their enrolees. This method entails giving enrolees advise on which physiotherapists to choose when they call customer service. Offering this advice as an extra service is supposed to improve service quality ratings. Objective of this study is to evaluate this channelling method on effectiveness and the impact on service quality ratings.MethodsIn this experiment, one of the health insurer's customer service call teams (pilot team) began advising enrolees on their choice of physiotherapist. Three data sources were used. Firstly, all enrolees who called customer service received an online questionnaire in order to measure their evaluation of the quality of service. Enrolees who were offered advice received a slightly different questionnaire which, in addition, asked about whether they intended to follow the advice they were offered. Multilevel regression analysis was conducted to analyse the difference in service quality ratings between the pilot team and two comparable customer service teams before and after the implementation of the channelling method. Secondly, employees logged each call, registering, if they offered advice, whether the enrolee accepted it, and if so, which care provider was advised. Thirdly, data from the insurance claims were used to see if enrolees visited the recommended physiotherapist.ResultsThe results of the questionnaire show that enrolees responded favorably to being offered advice on the choice of physiotherapist. Furthermore, 45% of enrolees who received advice and then went on to visit a care provider, followed the advice. The service quality ratings were higher compared to control groups. However, it could not be determined whether this effect was entirely due to the intervention.ConclusionsChannelling enrolees towards preferred care providers by offering advice on their choice of care provider when they call customer service is successful. The effect on service quality seems positive, although a causal relationship could not be determined.

Project description:Summary Gene-by-environment (GxE) interactions, in which a genetic variant’s phenotypic effect is condition specific, are fundamental for understanding fitness landscapes and evolution but have been difficult to identify at the single-nucleotide level. Although many condition-specific quantitative trait loci (QTLs) have been mapped, these typically contain numerous inconsequential variants in linkage, precluding understanding of the causal GxE variants. Here, we introduce BARcoded Cas9 retron precise parallel editing via homology (CRISPEY-BAR), a high-throughput precision genome editing strategy, and use it to map GxE interactions of naturally occurring genetic polymorphisms impacting yeast growth. We identified hundreds of GxE variants within condition-specific QTLs, revealing unexpected genetic complexity. Moreover, we found that 93.7% of non-neutral natural variants within ergosterol biosynthesis pathway genes showed GxE interactions, including many impacting antifungal drug resistance through diverse molecular mechanisms. In sum, our results suggest an extremely complex, context-dependent fitness landscape characterized by pervasive GxE interactions while also demonstrating massively parallel genome editing as an effective means for investigating this complexity. Graphical abstract Highlights • CRISPEY-BAR precisely measures effects of single genetic variants in high throughput• Pooled competition of barcoded strains maps condition-specific (GxE) fitness effects• Editing more than 4,000 natural genetic variants reveals pervasive GxE and molecular mechanisms• Many natural GxE variants in the ergosterol pathway lead to antifungal drug resistance Chen et al. introduce CRISPEY-BAR, a method to precisely measure individual genetic variant effects through massively parallel genome editing. Editing more than 4,000 natural genetic variants in yeast, they found pervasive condition-specific effects known as gene-by-environment (GxE) interactions. The single-nucleotide resolution revealed many GxE variants underlying antifungal drug resistance and their molecular mechanisms.

Dataset Information

Gene-environment correlation: difficulties and a natural experiment-based strategy.

Publications

Gene-environment correlation: difficulties and a natural experiment-based strategy.

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