Evidence map›Paper›PMID 29555026›Full record

ReviewMutation research. Reviews in mutation research

Assessing health risks from multiple environmental stressors: Moving from G×E to I×E.

Cliona M McHale, Gwendolyn Osborne, Rachel Morello-Frosch, Andrew G Salmon, Martha S Sandy, Gina Solomon, Luoping Zhang, Martyn T Smith, Lauren Zeise

Open access · greenAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Mutation research. Reviews in mutation research. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
1.6field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. FIGO committee opinion: Environmental drivers of obstetric health and early childhood development.International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics · 2025
    Article
  4. FIGO committee opinion: Environmental drivers of gynecologic and reproductive health.International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics · 2025
    Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. Review
  11. The Exposome and Toxicology: A Win-Win Collaboration.Toxicological sciences : an official journal of the Society of Toxicology · 2022
    Review
  12. Review
  13. Estimated Cancer Risks Associated with Nitrosamine Contamination in Commonly Used Medications.International journal of environmental research and public health · 2021
    Article
  14. Article
  15. Article
  16. Review
  17. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Cliona M McHaleSuperfund Research Center, School of Public Health, University of California, Berkeley, CA 94720, USA. Electronic address: cmchale@berkeley.edu.
Gwendolyn OsborneOffice of Environmental Health Hazard Assessment, California Environmental Protection Agency, Oakland, CA 94612, USA.
Rachel Morello-FroschSuperfund Research Center, School of Public Health, University of California, Berkeley, CA 94720, USA; Department of Environmental Science, Policy and Management, University of California, Berkeley, CA 94720, USA.
Andrew G SalmonOffice of Environmental Health Hazard Assessment, California Environmental Protection Agency, Oakland, CA 94612, USA.
Martha S SandyOffice of Environmental Health Hazard Assessment, California Environmental Protection Agency, Oakland, CA 94612, USA.
Gina SolomonCalifornia Environmental Protection Agency, Sacramento, CA 95814, USA.
Luoping ZhangSuperfund Research Center, School of Public Health, University of California, Berkeley, CA 94720, USA.
Martyn T SmithSuperfund Research Center, School of Public Health, University of California, Berkeley, CA 94720, USA.
Lauren ZeiseOffice of Environmental Health Hazard Assessment, California Environmental Protection Agency, Oakland, CA 94612, USA.
California Environmental Protection Agency · USUniversity of California, Berkeley · US

Funding

Training CoreP42ES004705 · NIEHS · UNIVERSITY OF CALIFORNIA BERKELEY · PI MORELLO-FROSCH, RACHEL ADELE · 1987 to 2025
$74.6M
The UCSF Pregnancy Exposures to Environmental Chemicals (PEEC) Children's CenterP01ES022841 · NIEHS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WOODRUFF, TRACEY J. · 2013 to 2018
$3.9M
NIEHS NIH HHS P01 ES022841NIEHS NIH HHS P42 ES004705
6 · The paper itself

Abstract

Research on disease causation often attempts to isolate the effects of individual factors, including individual genes or environmental factors. This reductionist approach has generated many discoveries, but misses important interactive and cumulative effects that may help explain the broad range of variability in disease occurrence observed across studies and individuals. A disease rarely results from a single factor, and instead results from a broader combination of factors, characterized here as intrinsic (I) and extrinsic (E) factors. Intrinsic vulnerability or resilience emanates from a variety of both fixed and shifting biological factors including genetic traits, while extrinsic factors comprise all biologically-relevant external stressors encountered across the lifespan. The I×E concept incorporates the multi-factorial and dynamic nature of health and disease and provides a unified, conceptual basis for integrating results from multiple areas of research, including genomics, G×E, developmental origins of health and disease, and the exposome. We describe the utility of the I×E concept to better understand and characterize the cumulative impact of multiple extrinsic and intrinsic factors on individual and population health. New research methods increasingly facilitate the measurement of multifactorial and interactive effects in epidemiological and toxicological studies. Tiered or indicator-based approaches can guide the selection of potentially relevant I and E factors for study and quantification, and exposomics methods may eventually produce results that can be used to generate a response function over the life course. Quantitative data on I×E interactive effects should generate a better understanding of the variability in human response to environmental factors. The proposed I×E concept highlights the role for broader study design in order to identify extrinsic and intrinsic factors amenable to interventions at the individual and population levels in order to enhance resilience, reduce vulnerability and improve health.

Indexed as

Gene-Environment InteractionModels, GeneticStress, PhysiologicalAnimalsHumansRisk FactorsEpidemiologyExposomeGene-environment interactionsRiskSocial determinants of healthToxic chemical exposure

Identifiers

PMID29555026
PMCPMC5863617
OpenAlexW2771051242

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.