Ritchie SC, Kettunen J, Brozynska M, et al. - Researchers sought to determine the contributions of five circulating glycoproteins—alpha-1 antitrypsin (AAT), alpha-1-acid glycoprotein (AGP), haptoglobin (HP), transferrin (TF), and alpha-1-antichymotrypsin—to the disease and mortality risks predicted by GlycA. Imputation models were trained for AAT, AGP, HP, and TF from nuclear magnetic resonance (NMR) metabolite measurements in 626 adults from a population cohort with matched NMR and immunoassay data. In 11,861 adults from two population cohorts with 8 years of follow-up, they estimated levels of AAT, AGP, and HP. For AAT, AGP, and HP but not for TF, they obtained accurate imputation models. While the strongest correlation of AGP with GlycA was observed, this analysis revealed the most predictive value of variation in imputed AAT levels for morbidity and mortality for the widest range of diseases over the 8-year follow-up period, including heart failure (meta-analysis hazard ratio = 1.60 per standard deviation increase of AAT), influenza and pneumonia (HR = 1.37), and liver diseases (HR = 1.81). As per transcriptional analyses, an association of elevated AAT with diverse inflammatory immune pathways was noted.