Instrumental variable (IV) strategies are widely used to estimate causal effects in economics,
political science, epidemiology, sociology, psychology, and other fields. When there is
unobserved heterogeneity in causal effects, standard linear IV estimators only represent
effects for complier subpopulations (Imbens and Angrist, 1994). Marginal treatment effect
(MTE) methods (Heckman and Vytlacil, 1999, 2005) allow researchers to use additional
assumptions to extrapolate beyond complier subpopulations. We discuss a flexible framework
for MTE methods based on linear regression and the generalized method of moments. We
show how to implement the framework using the ivmte package for R.
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Response to Valle and Zorello Laporta: Clarifying the Use of Instrumental Variable Methods to Understand the Effects of Environmental Change on Infectious Disease Transmission
ABSTRACT. Identifying the effects of environmental change on the transmission of vectorborne and zoonotic diseases is of fundamental importance in the face of rapid global change. Causal inference approaches, including instrumental variable (IV) estimation, hold promise in disentangling plausibly causal relationships from observational data in these complex systems. Valle and Zorello Laporta recently critiqued the application of such approaches in our recent study of the effects of deforestation on malaria transmission in the Brazilian Amazon on the grounds that key statistical assumptions were not met. Here, we respond to this critique by 1) deriving the IV estimator to clarify the assumptions that Valle and Zorello Laporta conflate and misrepresent in their critique, 2) discussing these key assumptions as they relate to our original study and how our original approach reasonably satisfies the assumptions, and 3) presenting model results using alternative instrumental variables that can be argued more strongly satisfy key assumptions, illustrating that our results and original conclusion—that deforestation drives malaria transmission—remain unchanged.
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- Award ID(s):
- 2011147
- NSF-PAR ID:
- 10334205
- Date Published:
- Journal Name:
- The American Journal of Tropical Medicine and Hygiene
- Volume:
- 105
- Issue:
- 6
- ISSN:
- 0002-9637
- Page Range / eLocation ID:
- 1456 to 1459
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract Mosquito‐borne diseases cause a major burden of disease worldwide. The vital rates of these ectothermic vectors and parasites respond strongly and nonlinearly to temperature and therefore to climate change. Here, we review how trait‐based approaches can synthesise and mechanistically predict the temperature dependence of transmission across vectors, pathogens, and environments. We present 11 pathogens transmitted by 15 different mosquito species – including globally important diseases like malaria, dengue, and Zika – synthesised from previously published studies. Transmission varied strongly and unimodally with temperature, peaking at 23–29ºC and declining to zero below 9–23ºC and above 32–38ºC. Different traits restricted transmission at low versus high temperatures, and temperature effects on transmission varied by both mosquito and parasite species. Temperate pathogens exhibit broader thermal ranges and cooler thermal minima and optima than tropical pathogens. Among tropical pathogens, malaria and Ross River virus had lower thermal optima (25–26ºC) while dengue and Zika viruses had the highest (29ºC) thermal optima. We expect warming to increase transmission below thermal optima but decrease transmission above optima. Key directions for future work include linking mechanistic models to field transmission, combining temperature effects with control measures, incorporating trait variation and temperature variation, and investigating climate adaptation and migration.
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Background Properly adjusting for unmeasured confounders is critical for health studies in order to achieve valid testing and estimation of the exposure’s causal effect on outcomes. The instrumental variable (IV) method has long been used in econometrics to estimate causal effects while accommodating the effect of unmeasured confounders. Mendelian randomization (MR), which uses genetic variants as the instrumental variables, is an application of the instrumental variable method to biomedical research fields, and has become popular in recent years. One often‐used estimator of causal effects for instrumental variables and Mendelian randomization is the two‐stage least square estimator (TSLS). The validity of TSLS relies on the accurate prediction of exposure based on IVs in its first stage.
Results In this note, we propose to model the link between exposure and genetic IVs using the least‐squares kernel machine (LSKM). Some simulation studies are used to evaluate the feasibility of LSKM in TSLS setting.
Conclusions Our results show that LSKM based on genotype score or genotype can be used effectively in TSLS. It may provide higher power when the association between exposure and genetic IVs is nonlinear.
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Abstract Instrumental variables have been widely used to estimate the causal effect of a treatment on an outcome. Existing confidence intervals for causal effects based on instrumental variables assume that all of the putative instrumental variables are valid; a valid instrumental variable is a variable that affects the outcome only by affecting the treatment and is not related to unmeasured confounders. However, in practice, some of the putative instrumental variables are likely to be invalid. This paper presents two tools to conduct valid inference and tests in the presence of invalid instruments. First, we propose a simple and general approach to construct confidence intervals based on taking unions of well‐known confidence intervals. Second, we propose a novel test for the null causal effect based on a collider bias. Our two proposals outperform traditional instrumental variable confidence intervals when invalid instruments are present and can also be used as a sensitivity analysis when there is concern that instrumental variables assumptions are violated. The new approach is applied to a Mendelian randomization study on the causal effect of low‐density lipoprotein on globulin levels.
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Phenotypes are used for a multitude of purposes such as defining species, reconstructing phylogenies, diagnosing diseases or improving crop and animal productivity, but most of this phenotypic data is published in free-text narratives that are not computable. This means that the complex relationship between the genome, the environment and phenotypes is largely inaccessible to analysis and important questions related to the evolution of organisms, their diseases or their response to climate change cannot be fully addressed. It takes great effort to manually convert free-text narratives to a computable format before they can be used in large-scale analyses. We argue that this manual curation approach is not a sustainable solution to produce computable phenotypic data for three reasons: 1) it does not scale to all of biodiversity; 2) it does not stop the publication of free-text phenotypes that will continue to need manual curation in the future and, most importantly, 3) It does not solve the problem of inter-curator variation (curators interpret/convert a phenotype differently from each other). Our empirical studies have shown that inter-curator variation is as high as 40% even within a single project. With this level of variation, it is difficult to imagine that data integrated from multiple curation projects can be of high quality. The key causes of this variation have been identified as semantic vagueness in original phenotype descriptions and difficulties in using standardised vocabularies (ontologies). We argue that the authors describing phenotypes are the key to the solution. Given the right tools and appropriate attribution, the authors should be in charge of developing a project’s semantics and ontology. This will speed up ontology development and improve the semantic clarity of phenotype descriptions from the moment of publication. A proof of concept project on this idea was funded by NSF ABI in July 2017. We seek readers input or critique of the proposed approaches to help achieve community-based computable phenotype data production in the near future. Results from this project will be accessible through https://biosemantics.github.io/author-driven-production.more » « less
- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.4269/ajtmh.21-0218
