Gene-environment interactions and the effect on obesity risk in low and middle-income countries: a scoping review.

Background: Obesity represents a major and preventable global health challenge as a complex disease and a modifiable risk factor for developing other non-communicable diseases. In recent years, obesity prevalence has risen more rapidly in low- and middle-income countries (LMICs) compared to high-income countries (HICs). Obesity traits are shown to be modulated by an interplay of genetic and environmental factors such as unhealthy diet and physical inactivity in studies from HICs focused on populations of European descent; however, genetic heterogeneity and environmental differences prevent the generalisation of study results to LMICs. Primary research investigating gene-environment interactions (GxE) on obesity in LMICs is limited but expanding. Synthesis of current research would provide an overview of the interactions between genetic variants and environmental factors that underlie the obesity epidemic and identify knowledge gaps for future studies. Methods: Three databases were searched systematically using a combination of keywords such as "genes", "obesity", "LMIC", "diet", and "physical activity" to find all relevant observational studies published before November 2022. Results: Eighteen of the 1,373 articles met the inclusion criteria, of which one was a genome-wide association study (GWAS), thirteen used a candidate gene approach, and five were assigned as genetic risk score studies. Statistically significant findings were reported for 12 individual SNPs; however, most studies were small-scale and without replication. Conclusion: Although the results suggest significant GxE interactions on obesity in LMICs, updated robust statistical techniques with more precise and standardised exposure and outcome measurements are necessary for translatable results. Future research should focus on improved quality replication efforts, emphasising large-scale and long-term longitudinal study designs using multi-ethnic GWAS.