Multiomics Picture of Obesity in Young Adults.

Obesity is a socially significant disease that is characterized by a disproportionate accumulation of fat. It is also associated with chronic inflammation, cancer, diabetes, and other comorbidities. Investigating biomarkers and pathological processes linked to obesity is especially vital for young individuals, given their increased potential for lifestyle modifications. By comparing the genetic, proteomic, and metabolomic profiles of individuals categorized as underweight, normal, overweight, and obese, we aimed to determine which omics layer most accurately reflects the phenotypic changes in an organism that result from obesity. We profiled blood plasma samples by employing three omics methodologies. The untargeted GC×GC-MS metabolomics approach identified 313 metabolites. To augment the metabolomic dataset, we integrated a label-free HPLC-MS/MS proteomics method, leading to the identification of 708 proteins. The genomic layer encompassed the genotyping of 647,250 SNPs. Utilizing omics data, we trained sparse Partial Least Squares models to predict body mass index. Molecular features exhibiting frequently non-zero coefficients were selected as potential biomarkers, and we further explored enriched biological pathways. Proteomics was the most effective in single-omics analyses, with a median absolute error (MAE) of 5.44 ± 0.31 kg/m 2 , incorporating an average of 24 proteins per model. Metabolomics showed slightly lower performance (MAE = 6.06 ± 0.33 kg/m 2 ), followed by genomics (MAE = 6.20 ± 0.34 kg/m 2 ). As expected, multiomic models demonstrated better accuracy, particularly the combination of proteomics and metabolomics (MAE = 4.77 ± 0.33 kg/m 2 ), while including genomics data did not enhance the results. This manuscript is the first multiomics study of obesity in a gender-balanced cohort of young adults profiled by genomic, proteomic, and metabolomic methods. The comprehensive approach provides novel insights into the molecular mechanisms of obesity, opening avenues for more targeted interventions.