B4417 - Evaluation of polygenic risk scores and development of integrated risk tools across the life course - 25/10/2023

B number: 
B4417
Principal applicant name: 
Vincent Plagnol | Genomics plc (United Kingdom)
Co-applicants: 
Rachel Moore, Jamie Floyd, Jamie Hall, Charlie Hatcher, Edward Beard, Sophie Landon, William Tarran, Deborah Thompson, Melisa Chuong, Daniel Wells
Title of project: 
Evaluation of polygenic risk scores and development of integrated risk tools across the life course
Proposal summary: 

Polygenic risk scores (PRSs) aggregate genetic data across the genome and summarise these data into a single number that quantifies an individual’s genetically defined disease risk. PRSs can also be used to predict standard outcomes that are relevant to health, such as height or weight. Genomics plc has built a range of tools to generate the most accurate PRS library, and combine these PRSs with other non-genetic factors into integrated risk tools (IRT). However, typical PRS and IRT evaluation focuses on adulthood. As a result, we have a limited understanding of how these tools perform across the life course, especially at which age genetically driven differences become apparent. Similarly, little is known of how the combination of PRS and early life data can jointly predict adult outcomes, which is key for preventative opportunities that need to occur at an early age.
ALSPAC has generated unique data across the life course of individuals. These data provide an opportunity to understand the interplay between childhood and adult data together with genetics. We therefore are proposing to use the ALSPAC data to understand the role of PRSs in the context of an individual life’s course, with a focus not only on prediction accuracy but also on how the accuracy of these predictions varies with age and when they have the greatest utility. We will further explore whether childhood information, together with immutable genetic data, can be combined to accurately predict traits in adulthood, thus providing an effective lever for triggering health interventions that are most useful during childhood.

Impact of research: 
We anticipate that this project will enable us to better quantify our predictions of health outcomes and trait values, with and without early life information. This information will improve our understanding of the contribution of the genetic information captured by PRS to risk/trait prediction at each stage of the life course, and will hence provide clarity around the potential benefits that could be conferred by the appropriate use of PRS at different points in an individual’s life.
Date proposal received: 
Monday, 18 September, 2023
Date proposal approved: 
Thursday, 21 September, 2023
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Bone disorders - arthritis, osteoporosis, Cancer, Diabetes, Eczema, Gastrointestinal, Hypertension, Infection, Obesity, Respiratory - asthma, General quantitative traits, such as weight, BMI, height, blood pressure , GWAS, Statistical methods, Polygenic risk scores, Blood pressure, BMI, Cardiovascular, Genetic epidemiology, Genetics, Genomics, Genome wide association study, Growth, Metabolic - metabolism, Statistical methods