Decode Genetics publishes largest study of the plasma proteome

By Andre Rickard, The Science Advisory Board contributing writer

December 3, 2021 -- In a study published December 2 in Nature Genetics, scientists at Decode Genetics, a subsidiary of pharmaceutical company Amgen, demonstrated how measuring levels of several proteins in plasma at population scale combined with data on sequence diversity and RNA expression dramatically increases insights into human diseases and other phenotypes.

Scientists at Decode Genetics used the levels of 5,000 proteins in plasma targeted on a multiplex platform at population scale to unravel their genetic determinants and their relationship to human disease and other traits. Previous studies of the genetics of protein levels either consisted of much fewer individuals or tested far fewer proteins than this study.

Using protein levels in plasma measured with the SomaScan proteomics assay, scientists tested the association of 27 million sequence variants with the plasma levels of 4,719 proteins in 35,559 Icelanders. They found 18,084 associations between variants in the sequence and the levels of proteins in plasma, where 19% were with rare variants identified with whole-genome sequencing. Overall, 93% of the associations were novel.

Additionally, they replicated 83% and 64% of the reported associations from the largest existing plasma proteomic studies based on the SomaScan method and the antibody-based Olink assay, respectively. The levels of proteins in plasma were tested for associations with 373 diseases and other traits and yielded 257,490 such associations.

Researchers integrated associations of sequence variants with protein levels and diseases and other traits and found that 12% of approximately 50,0000 variants reported to associate with diseases and other traits also associate with protein levels.

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