posted on 2020-05-08, 17:22authored byAda AdminAda Admin, Valborg Gudmundsdottir, Shaza B Zaghlool, Valur Emilsson, Thor Aspelund, Marjan Ilkov, Elias F Gudmundsson, Stefan M Jonsson, Nuno R Zilhão, John R Lamb, Karsten Suhre, Lori L Jennings, Vilmundur Gudnason
increasing prevalence of type 2 diabetes poses a major challenge to societies
worldwide. 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 4,137
proteins in 5,438 elderly Icelanders and identified 536 proteins associated
with prevalent and/or incident type 2 diabetes. We validated a subset of the
observed associations in an independent case-control study of type 2 diabetes. These
protein associations provide novel biological insights into the molecular
mechanisms that are dysregulated prior to and following the onset of type 2
diabetes and can be detected in serum. A bi-directional two-sample Mendelian
randomization analysis indicated that serum changes of at least 23 proteins are
downstream of the disease or its genetic liability, while 15 proteins were
supported as having a causal role in type 2 diabetes.
The study was funded by the Icelandic Heart Association, National Institute of Aging contracts (N01-AG-12100 and HHSN271201200022C) and Althingi (the Icelandic Parliament). Va.G. is supported by the Icelandic Centre for Research (grant no. 184845-051). Work on the QMDiab cohort was supported by the Biomedical Research Program at Weill Cornell Medicine in Qatar, a program funded by the Qatar Foundation. K.S. is also supported by QNRF grant NPRP11C-0115-180010.