Our work on the genomic architecture of circulating cytokines is now published in Communications Biology
🔈 Our genome-wide association study of circulating levels of 40 cytokines in 75,000 individuals is now out ‼️
We ran a meta-analysis across 3 datasets:
👉 SCALLOP (Olink-based quantifications)
👉 deCODE (SomaScan-based)
👉 3 Finnish cohorts (YFS, FINRISK 1997 & 2002, Luminex-based)
Some topline findings 📊
1️⃣ Across the three datasets, SCALLOP (Olink) showed the lowest number of significant hits, but these hits had the highest reproducibility rates in the other datasets
2️⃣ When pooling the GWAS datasets with meta-analyses, we found SNPs in 169 loci associated with at least one cytokine — 156 of them were novel
3️⃣ There was a strong negative correlation between minimum allele frequency and effect size — cis-acting variants had larger efffects on cytokine levels than trans-variants
4️⃣ TWAS-MR using whole blood eQTLs revealed interesting insights, e.g.:
👉 the effect of variants influencing the expression of the scavenger receptor ACKR1 on multiple chemokines
👉the effect of variants influencing the expression of TRAFD1 (an adaptor protein binding to TNF receptors) on multiple downstream cytokines
5️⃣ The levels of most cytokines were genetically correlated with cis-Mendelian randomization revealing complex interconnections of genetically proxied cytokine levels — TNF-b, VEGF, and IL-1ra exhibited pleiotropic downstream effects on multiple cytokines
6️⃣ As cytokines are typically investigated as promising drug targets for multiple diseases with inflammatory pathogenesis, we ran cis-Mendelian randomization and colocalization for different disease outcomes. We found strongest evidence (cis-MR, coloc, external MR replication, observational analyses) for:
👉G-CSF/CSF-3 as a target for asthma
👉CXCL9/MIG as a target for Crohn’s disease
🔗 Link to the paper: https://www.nature.com/articles/s42003-025-07453-w
The summary statistics of the GWAS meta-analyses are available through GWAS Catalog (https://www.ebi.ac.uk/gwas/ accession numbers: GCST90428399–GCST90428438)
We hope it will be a useful resource for focused cytokine genetics research ❗
Many thanks to Marek Konieczny, Murad Omarov and Lanyue Zhang, who ran most analyses, and of course all co-authors.
