Design and methodology challenges of environment-wide association studies: A systematic review

Zheng, Yi; Chen, Zhaoyi; Pearson, Thomas A.; Zhao, Jinying; Hu, Hui; Prosperi, Mattia

doi:10.1016/j.envres.2020.109275

Cited by 45 publications

(25 citation statements)

References 62 publications

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“…The eco-exposome concept-Environmental Toxicology and Chemistry, 2022;41:30-45 eco-and human exposome research (Collette et al, 2019;Jeong et al, 2018;Rappaport, 2012;Zheng et al, 2020). For example, Collette et al (2019) used PLS combined with crossvalidated predictive residuals analyses to identify stressors related to endogenous metabolite profiles in a zebrafish cell line exposed to water sample extracts from 38 different US streams.…”

Section: Making the Link Between Exposure And Effectmentioning

confidence: 99%

The Eco‐Exposome Concept: Supporting an Integrated Assessment of Mixtures of Environmental Chemicals

Scholz

Nichols

Escher

et al. 2021

Enviro Toxic and Chemistry

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Organisms are exposed to ever-changing complex mixtures of chemicals over the course of their lifetime. The need to more comprehensively describe this exposure and relate it to adverse health effects has led to formulation of the exposome concept in human toxicology. Whether this concept has utility in the context of environmental hazard and risk assessment has not been discussed in detail. In this Critical Perspective, we propose-by analogy to the human exposometo define the eco-exposome as the totality of the internal exposure (anthropogenic and natural chemicals, their biotransformation products or adducts, and endogenous signaling molecules that may be sensitive to an anthropogenic chemical exposure) over the lifetime of an ecologically relevant organism. We describe how targeted and nontargeted chemical analyses and bioassays can be employed to characterize this exposure and discuss how the adverse outcome pathway concept could be used to link this exposure to adverse effects. Available methods, their limitations, and/or requirement for improvements for practical application of the eco-exposome concept are discussed. Even though analysis of the eco-exposome can be resource-intensive and challenging, new approaches and technologies make this assessment increasingly feasible. Furthermore, an improved understanding of mechanistic relationships between external chemical exposure(s), internal chemical exposure(s), and biological effects could result in the development of proxies, that is, relatively simple chemical and biological measurements that could be used to complement internal exposure assessment or infer the internal exposure when it is difficult to measure.

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Section: Making the Link Between Exposure And Effectmentioning

confidence: 99%

The Eco‐Exposome Concept: Supporting an Integrated Assessment of Mixtures of Environmental Chemicals

Scholz

Nichols

Escher

et al. 2021

Enviro Toxic and Chemistry

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“…However, much larger sample sizes are needed for the detection of interactions compared to marginal effect sample sizes. In addition, the complexity of measuring the environmental exposure, the difficulty of incorporating environmental measures to the models, the heterogeneity of the environmental exposures, and the lack of publicly available data represent important hurdles that limit the advancement of this field of study [99,100,[105][106][107].…”

Section: Gene-gene Interactions (Gxg) and Genomic Variant Epistasismentioning

confidence: 99%

In Search of Complex Disease Risk through Genome Wide Association Studies

et al. 2021

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The identification and characterisation of genomic changes (variants) that can lead to human diseases is one of the central aims of biomedical research. The generation of catalogues of genetic variants that have an impact on specific diseases is the basis of Personalised Medicine, where diagnoses and treatment protocols are selected according to each patient’s profile. In this context, the study of complex diseases, such as Type 2 diabetes or cardiovascular alterations, is fundamental. However, these diseases result from the combination of multiple genetic and environmental factors, which makes the discovery of causal variants particularly challenging at a statistical and computational level. Genome-Wide Association Studies (GWAS), which are based on the statistical analysis of genetic variant frequencies across non-diseased and diseased individuals, have been successful in finding genetic variants that are associated to specific diseases or phenotypic traits. But GWAS methodology is limited when considering important genetic aspects of the disease and has not yet resulted in meaningful translation to clinical practice. This review presents an outlook on the study of the link between genetics and complex phenotypes. We first present an overview of the past and current statistical methods used in the field. Next, we discuss current practices and their main limitations. Finally, we describe the open challenges that remain and that might benefit greatly from further mathematical developments.

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“…In other words, the traditional hypothesis-driven approaches, targeting few exposures or chemicals, are replaced by large panels of exposure candidates. To tackle the exposome challenge and analogously to the genomic field, environment-wide association studies (EWAS) have been appearing during the last decade applied to metabolic diseases, preterm birth, reproductive function, or cancer, among others [21]. This conception realigns the epidemiological design around the individual profiling and its exposure-disease continuum of biomarkers, boosting the hypothesis generation from the order of some few exposures to large panels of hundreds or thousands.…”

Section: Mycotoxin Biomarkers In Exposome-health Studiesmentioning

confidence: 99%