Multiomics reveal key inflammatory drivers of severe obesity: IL4R, LILRA5, and OSM.

Polygenic severe obesity (body mass index [BMI] ≥40 kg/m) has increased, especially in Hispanic/Latino populations, yet we know little about the underlying mechanistic pathways. We analyzed whole-blood multiomics data to identify genes differentially regulated in severe obesity in Mexican Americans from the Cameron County Hispanic Cohort. Our RNA sequencing analysis identified 124 genes significantly differentially expressed between severe obesity cases (BMI ≥40 kg/m) and controls (BMI <25 kg/m); 33% replicated in an independent sample from the same population.