Developing the next generation of effective medicines will require approaches that deliver actionable insights into the biological processes and pathways underlying human health and disease. Protein biomarkers are increasingly utilized to stratify patients, predict outcomes and responses, and deepen our understanding of disease pathophysiology. Proteins represent the best real-time markers of dynamic biological processes, but they are not sufficient for researchers to assign a cause-and-effect relationship to the parameter(s) being studied. This issue can be addressed by combining genomics and proteomics to identify protein quantitative trait loci (pQTLs)—genetic variants linked to protein expression levels. Variants proximal to the gene encoding the protein (cis-pQTLs) can be used in combination with associated clinical parameters in Mendelian randomization analysis to identify proteins with a high probability of causal involvement in the disease being studied—proteins that could represent novel drug targets. Additionally, genetic variants distal to the protein-coding genes (trans-pQTLs) can reveal novel molecular connections and pathways involved in disease. The SCALLOP consortium, made up of 28 principal investigators from 25 research institutes, is a collaborative framework for the discovery and follow-up of genetic associations with proteins. Speakers from SCALLOP will discuss how enabling technologies are allowing proteogenomic studies to be performed on a scale not previously possible, and will provide examples of such studies, including one assessing links between angiotensin-converting enzyme 2 (ACE2) expression and COVID-19.

• Learn about the SCALLOP consortium’s mission and vision to probe the genetics of the human proteome
• Discover the genetic architecture of 184 circulating proteins related to human disease
• Hear how genetically predicted ACE2 levels relate to COVID-19 severity.

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