Gudmundsdottir , Valborg, Emilsson, Valur, Aspelund, Thor, Ilkov, Marjan, Gudmundsson, Elias F, Zilhao, Nuno, Lamb, John, Jennings, Lori and Gudnason, Vilmundur (2019) Deep serum proteomics reveals biomarkers for prevalent and incident T2DM. Nature communications.

Abstract

The prevalence of type 2 diabetes mellitus (T2DM) is expected to increase rapidly in the next decades, posing a major challenge to societies worldwide1. The emerging era of precision medicine calls for the discovery of biomarkers of clinical value for prediction of disease onset, where causal biomarkers can furthermore provide actionable targets. Blood-based factors like serum proteins are in contact with every organ in the body to mediate global homeostasis and may thus directly regulate complex processes such as aging and the development of common chronic diseases. We applied a data-driven proteomics approach measuring serum levels of 4192 proteins in 5457 Icelanders to discover novel biomarkers for incident T2DM and further describe the serum protein profile of prevalent T2DM. We identified 537 proteins associated with incident or prevalent T2DM and, through LASSO penalized logistic regression analysis combined with bootstrap resampling, a panel of 20 protein biomarkers that accurately predicted incident T2DM was identified with a significant incremental improvement over traditional risk factors. Finally, a Mendelian randomization analysis provided additional support for a causal role of 51 proteins in the development of T2DM, which could be of particular interest as novel therapeutic targets.

Item Type:	Article
Date Deposited:	04 Jun 2019 00:45
Last Modified:	04 Jun 2019 00:45
URI:	https://oak.novartis.com/id/eprint/38367