Large study connects gene variants, proteins levels and disease

The link between genetic variants, circulating blood protein levels and their association with disease has been investigated in one of the largest studies to date.

The study - which was funded and carried out by the Pharma Proteomics Project, a collaboration between UK Biobank and 13 biopharmaceutical companies - aims to accelerate genetics-guided drug discovery. Key findings so far include the identification of genetic variants that could influence susceptibility to diseases such as COVID-19, inflammatory bowel disease and cardiovascular disease.

The consortium behind the study has also has created an open-access interactive web resource, enabling other researchers to access summaries of protein and genomic profiling data. Raw data will be made available to researchers on request.

'This dataset will help paint a much more nuanced and detailed picture of how the human genome and proteins circulating in the blood influence human health and disease – enabling biomedical researchers to identify new biological associations, find new drug targets and build blood-based diagnostics' said the project's chair, Dr Chris Whelan from Janssen Research and Development in Boston, Massachusetts.

Publishing their results in Nature, the researchers quantified 2923 unique plasma proteins from 54,219 participants within UK Biobank. These results were analysed with whole genome data from the participants to identify genetic variants that influence how much of a particular protein is made.

When a set of genetic variants is associated with a change in protein level, their location on the chromosome is named a protein quantitative trait locus (pQTL). Of the 14,287 PQTLs identified in this study, 81 percent had not been previously reported. Of these, 1955 are thought to affect protein levels in a way that leads to disease. These pQTLs are of particular interest, as they are potential therapeutic targets.

'I am excited for researchers to use these data to identify patterns that could transform our understanding of how diseases develop, and to identify potential new treatment pathways,' said Professor Naomi Allen, chief scientist at UK Biobank.