Research collaboration offers new polygenic score insights in type 2 diabetes and related co-morbidities
An on-campus collaboration between NIHR Cambridge BRC-funded researchers, the University of Cambridge and AstraZeneca has had its research published in the journal Nature Communications.
In the study Identification of plasma proteomic markers underlying polygenic risk of type 2 diabetes and related comorbidities, a team of researchers led by NIHR Cambridge BRC Data Science & Population Health Theme Lead Professor Mike Inouye and Dr Dirk Paul, Senior Director at AstraZeneca, tested polygenic scores for type 2 diabetes and cardiometabolic comorbidities for associations with 2,922 circulating proteins in the UK Biobank.
Genomics can provide insight into the etiology of type 2 diabetes and its comorbidities, but assigning functionality to non-coding variants remains challenging.
Polygenic scores, which aggregate variant effects, can uncover mechanisms when paired with molecular data.
In this study, researchers found that genome-wide type 2 diabetes polygenic score associates with 617 proteins, of which 75% also associate with another cardiometabolic score. Partitioned type 2 diabetes scores, which capture distinct disease biology, associate with 342 proteins (20% unique).
They also identified key pathways (e.g., complement cascade), potential therapeutic targets (e.g., FAM3D in type 2 diabetes), and biomarkers of diabetic comorbidities (e.g., EFEMP1 and IGFBP2) through causal inference, pathway enrichment, and Cox regression of clinical trial outcomes.
The results are available for researchers to explore via an interactive open access portal.
Director of the NIHR Cambridge BRC Professor Miles Parkes said: “Congratulations to all involved in this study, it’s great to see a collaboration between the BRC, University of Cambridge and AstraZeneca coming to fruition and also to see the results being made available for other researchers.”
