We performed genome-proteome-wide association analysis for 4,775 human plasma proteins assayed by the SomaScan v4 platform among over 10,000 individuals, identifying 2,584 genomic regions associated with at least one out of 3,892 protein targets.
We deeply characterised cis-acting variants, including colocalisation with gene expression and alternative splicing events in multiple tissues and show their value for candidate causal gene assignment for established disease loci. In a phenome-wide colocalisation screen we identify a shared genetic architecture between 412 proteins targets and 506 curated traits establishing a proteomic-genomic map of human health.
Regional sentinel genetic variants associated (p<1.004x10-11) with at least one protein target in up to 10,708 participants from the Fenland Study. The lower panel maps the genomic locations of the genetic variants against the genomic locations of the protein-encoding genes. Genetic variants close to the protein-encoding gene (±500kb) are highlighted in pink (cis-pQTLs) and all others are shown in blue (trans-pQTLs). Darker shades indicate more significant p-values. The upper panel shows the number of associated protein targets for each genomic region (vertical line), with circles above representing the number of approximately independent genetic variants (R2<0.1), such that larger circles indicate more genetic variants in the region.