Measurement of the levels of a large number of proteins in plasma on a population scale when combined with data on sequence diversity and RNA expression exponentially increases knowledge about human diseases.
In a study published today in Nature Genetics, scientists at deCODE genetics have used levels of 5,000 plasma proteins targeted at a broad population scale to unravel their genetic determinants and their relationship to human disease and other traits.
deCODE: deciphering the disease
Proteomics can help solve one of the main challenges in genetic studies: determine which gene is responsible for the effect of a sequence variant in a disease.
Using plasma protein levels measured with the Somascan proteomics assay, deCODE genetics scientists tested the association of 27 million sequence variants with plasma levels of 4,719 proteins in 35,559 Icelanders. They found 18,084 associations between variants in the sequence and protein levels, where 19% are rare variants identified with whole genome sequencing.
In general, 93% of the associations are new. Furthermore, 83% and 64% of the associations reported from the largest existing plasma proteomic studies, based on the Somascan method and the antibody-based Olink assay, respectively, were replicated.
Protein levels in plasma were analyzed for associations with 373 diseases and other traits and 257,490 of such associations were obtained. They integrated associations of sequence variants with protein levels and disease and other traits, and found that 12% of around fifty thousand reported variants are associated with disease and other traits are also associated with protein levels.