Publication type
Journal Article
Authors
Publication date
August 3, 2026
Summary:
Background:
While genetic studies have identified hundreds of loci associated with adiposity, the phenotypic expression of this individual genetic risk is not fixed but dependent on environmental circumstances. Socioeconomic Position (SEP), which includes education, income, and area-level deprivation, serves as an important environmental modulator of genetic liability. However, the literature on Gene-Environment (G×E) interactions remains fragmented, particularly regarding how these evolve across the life course.
Aim:
Provide a comprehensive overview of available literature on how SEP factors relate to the effects of polygenic risk scores (PRS), genetic susceptibility, and epigenetic mechanisms in obesity.
Methods:
Following PRISMA guidelines, we searched five databases for human studies examining SEP, genetic or epigenetic markers, life course, and adiposity-related outcomes. In total, we synthesized 98 studies (79 genetic, 21 epigenetic, including two papers contributing to both domains) and assessed risk of bias using QUIPS.
Results:
Lower SEP, particularly lower educational attainment and greater area-level deprivation, was often associated with stronger genetic susceptibility to obesity, although findings differed by SEP component, life stage, PRS construction, outcome definition, ancestry, and analytical framework. Among the 29 studies formally testing genetic susceptibility-by-SEP interactions, PRS-size patterns were descriptive rather than indicating a clear hierarchy: large PRS produced the greatest number of formal interaction findings, while medium PRS showed a high proportion of significant findings in fewer and less comparable studies. Epigenetic analyses identified DNA methylation at stress-related and metabolic loci as a potential pathway linking socioeconomic disadvantage to obesity, though tissue specificity and causal direction remain limiting factors.
Conclusion:
Lower educational attainment and socioeconomic deprivation appear to amplify genetic susceptibility to obesity, although evidence remains heterogeneous in PRS construction, SEP operationalization, outcome definition, ancestry, and analytical framework. Emerging evidence suggests educational attainment and early-life socioeconomic conditions may represent modifiable contexts influencing genetic obesity risk across the life course.
Published in
International Journal of Obesity
DOI
https://doi.org/10.1038/s41366-026-02181-5
ISSN
3070565
Subjects
Notes
© The Author(s), under exclusive licence to Springer Nature Limited 2026
Online Early
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