Massive study on plasma proteome enhances understanding of human diseases

Recent research by investigators from deCODE genetics—a subsidiary of the pharmaceutical company Amgen—revealed how evaluating the levels of a huge number of proteins in plasma at a population scale when joined with data on sequence diversity and RNA expression drastically enhances the understanding of human diseases and other phenotypes. The research was published on December 2nd, 2021 in the Nature Genetics journal.

Massive study on plasma proteome enhances understanding of human diseases
Dr Kari Stefansson CEO of deCODE genetics and one of the senior authors on the paper. Image Credit: Copyright: deCODE genetics.

Researchers at deCODE genetics utilized levels of 5000 proteins in plasma directed on a multiplex platform at a population scale to reveal their genetic determinants and their relationship with human disease and other traits. Earlier works on the genetics of protein levels had lesser individuals or examined far fewer proteins compared to the current research.

With the help of protein levels in plasma analyzed with the Somascan proteomics assay, researchers at deCODE genetics investigated the link between 27 million sequence variants with plasma levels of 4,719 proteins in 35,559 Icelanders. The scientists discovered 18,084 connections between variants in the sequence and levels of proteins.

Around 19% had rare variants pinpointed with whole-genome sequencing. On the whole, 93% of the associations are new. Moreover, the researchers replicated 83% and 64% of the reported connections from the biggest existing plasma proteomic studies, on the basis of the Somascan method and the antibody-based Olink assay, respectively.

The levels of proteins in plasma were investigated for associations with 373 diseases and other traits and provided 257,490 such associations. The scientists integrated associations of sequence variants with protein levels and diseases and other traits and identified that 12% of about 50,000 variants reported to relate with diseases and other traits also relate with protein levels.

Proteomics can assist in solving one of the major challenges in genetic studies: to determine what gene is responsible for the effect of a sequence variant on a disease. In addition, the proteome provides some measure of time because levels of proteins in the blood rise and they fall as a function of time to and from events.

Kari Stefansson, Study Senior Author and CEO, deCODE Genetics

Journal reference:

Ferkingstad, E., et al. (2021) Large-scale integration of the plasma proteome with genetics and disease. Nature Genetics.


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