Both variants showed significant additive associations with type 2 diabetes and obesity. Importantly, the association with diabetes remained robust when participants were stratified by obesity status, suggesting the variant's link to diabetes is not explained solely by its effect on body weight. Statistical modeling helped pinpoint which variant drives the signal.

The two single nucleotide polymorphisms were in strong linkage disequilibrium, meaning they are inherited together more often than chance would predict. Conditional analyses, which test whether one variant explains away the association of the other, indicated that rs9939609 represents the primary association signal at this locus in this population. The study went beyond association testing to examine gene function.

In a subset of 152 participants, carriers of the rs9939609 risk allele showed significantly higher FTO messenger RNA expression in peripheral blood leukocytes, while rs1421085 showed no such expression difference. This finding raises the possibility that the variant acts through increased FTO expression, although the researchers measured expression in blood cells rather than metabolic tissues such as fat or pancreas. This study addresses that gap using population-specific diagnostic criteria and genetic modeling in a Thai cohort.

The authors note that the cross-sectional design, which measures genetic variants, disease status, and expression at a single point in time, precludes causal inference. The findings demonstrate an additive contribution of FTO variants to metabolic risk in Thai adults and highlight rs9939609 as the major genetic signal at this locus, potentially acting through increased FTO expression, but further work will be needed to establish mechanism and causality.

Subject of Research: Association of FTO intron-1 variants with type 2 diabetes, obesity, and FTO gene expression in Thai adults

Article Title: Genetic and expression evidence supports FTO rs9939609 as a key susceptibility marker for type 2 diabetes and obesity in Thai adults

Article References: Yaikwawong, M., Kamdee, K., Ek-eudomsuk, P., Sittithumcharee, G., Jirawatnotai, S., & Chuengsamarn, S. (2026). Genetic and expression evidence supports FTO rs9939609 as a key susceptibility marker for type 2 diabetes and obesity in Thai adults. Scientific Reports. https://doi.org/10.1038/s41598-026-77970-z

Image Credits: AI Generated

DOI: 10.1038/s41598-026-77970-z

Keywords: FTO, rs9939609, type 2 diabetes, obesity, Thai population, genetic association, mRNA expression, linkage disequilibrium, cardiometabolic risk, single nucleotide polymorphism, Genetic, expression