Scientific collaboration is driving population-scale proteogenomics
SCALLOP (Systematic and Combined AnaLysis of Olink Proteins) is an independent, collaborative framework for the discovery and follow-up of genetic associations with proteins for researchers generating data using the Olink platform. The aim of the SCALLOP consortium is to identify novel molecular connections and protein biomarkers that are causal in diseases, and to date, 35 PIs from 28 research institutions have joined the effort, which now comprises summary level data for almost 70,000 patients and controls from 45 cohort studies. This collaborative approach can greatly enhance the statistical power of studies through combined analysis.
In a landmark study, members of the consortium combined data to probe the genetic influences on inflammation-related proteins, providing important insights into the pathogenesis of immune-mediated diseases. GWAS data and plasma protein measurements using the Olink Target 96 Inflammation panel were obtained from 11 SCALLOP member cohorts, totaling 14,824 samples. Summary protein quantitative trait loci (pQTL) data was generated for each cohort separately and used to input into a multi-cohort meta-analysis and the data was evaluated using Mendelian Randomization (MR) in relation to multiple immunological diseases.
These results identify targets of existing drugs and provide a powerful resource to facilitate future drug target prioritization.
The meta-analysis identified 180 significant associations between 108 genomic regions and 70 proteins: 59 (33%) were cis-pQTLs and 121 (67%) trans-pQTLs. Overall, 31 pQTLs overlapped with GWAS hits for at least one immune-mediated disease, with 76 unique pQTL protein–disease associations in total. Applying MR identified 10 significant causal associations between protein levels and diseases that retained significance after additional filters were applied to account for confounding factors. These data identified pathways that are already the target of existing drugs, providing confirmation of the utility of the approach used, and also highlight new potential therapeutic targets for several different immune-mediated diseases.
About SCALLOP
Get more information about SCALLOP and see a brief video interview with the consortium founder, Dr. Anders Mälarstig (Pfizer & Karolinska Institute).
Read more about the consortium and its research on the SCALLOP community page.
Selected SCALLOP publications
Read selected studies showcasing how collaborative proteomics studies enable genetic assessment of protein causality and novel drug targets, enhancing genomics’ link to phenotype.