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Updated: May 24, 2025

A High-Throughput Multiplexed Screening for Type 1 Diabetes, Celiac Diseases, and COVID-19
Published on: July 5, 2022
Identification of plasma proteomic markers underlying polygenic risk of type 2 diabetes and related comorbidities
Douglas P Loesch1, Manik Garg2, Dorota Matelska2
1Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK. douglas.loesch@astrazeneca.com.
Abstract:
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. Here, we test polygenic scores for type 2 diabetes and cardiometabolic comorbidities for associations with 2,922 circulating proteins in the UK Biobank. The 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). In this work, we identify 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. Our results are available via an interactive portal ( https://public.cgr.astrazeneca.com/t2d-pgs/v1/ ).
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