A study of cardiovascular proteins in over 30 000 individuals
A major proteogenomic study from SCALLOP identifies >450 pQTLs and several novel potential drug targets
In an important new study published in Nature Metabolism, the SCALLOP consortium identified protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs (genetic variants linked to protein expression levels) for 85 proteins. The data was compiled from 15 cohorts (studies from consortium members), all of which used the original Olink panel designed for cardiovascular studies, Olink CVD I.
In addition to around 170 cis-pQTLs with genetic variants proximal to the genes encoding the affected proteins, many trans-pQTLs were also identified and mapped to regulatory pathways, which could be verified by orthogonal means in several cases. Mendelian Randomization was also applied to identify 11 proteins with novel causal evidence of links to human disease, which could be of interest for future drug target investigations.
Folkersen, L., Gustafsson, S., Wang, Q. et al.Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.Nat Metab2, 1135–1148 (2020). https://doi.org/10.1038/s42255-020-00287-2 Link
What the authors say
Dr. Anders Mälarstig, SCALLOP founder and one of the principle investigators on the article, had the following to say about this landmark study:
“At the start of the SCALLOP consortium, we didn’t know if combining human genetics with Olink proteomics would even be possible at this large-scale, much less whether our approach would yield new insights into disease biology. In light of this paper, I’m now predicting that we will see a next generation of effective medicines emerge from similar approaches – with carefully-conducted Mendelian randomization studies of protein biomarkers. The full credit for this work should go to the CVD-I writing group and the SCALLOP consortium members“.
Any questions or reprint requests regarding this article should be addressed to Anders Mälarstig
About the author
Anders Malarstig, PhD, is Director of Target Sciences at Pfizer Worldwide Research and Development, as well as an affiliate researcher at the Karolinska Institute.
At Pfizer, Dr. Mälarstig is responsible for developing and applying strategies for new drug targets and precision medicine. He is a founding member and principle contact for the SCALLOP consortium.