B3943 - Disease risk prioritisation in early life using polygenic risk profiles - 24/01/2022

B number: 
Principal applicant name: 
Tom Richardson | MRC Integrative Epidemiology Unit (IEU) (United Kingdom)
Ms Si Fang, Prof George Davey Smith, Professor Tom Gaunt
Title of project: 
Disease risk prioritisation in early life using polygenic risk profiles
Proposal summary: 

Polygenic risk score (PRS) have the potential to stratify individuals at high risk of disease. Using a PRS in conjunctioon with traditional risk factors has been shown to enhance the risk prediction of disease outcomes in multiple studies. Exploiting genetic variants associated with disease risk from multiple genome-wide association studies for different risk factors and disease have been reported to outperform single-disease PRS. We hypothesis that with the inclusion of genetic variants associated with modifiable risk factors and biomarkers for disease onset and progression, PRS may provide enhanced risk stratification before the presence of risk factors and enable disease prevention in early life.

In this study, we will develop both single and multi-trait PRS models for complex traits in the UK Biobank and validate their performance in terms of prediction and stratification over the life course using data from participants in the ALSPAC cohort study.

Impact of research: 
We hope to be able to demonstrate that using human genetics can be a powerful approach to prioritising individuals at elevated disease risk during early stages in the lifecourse. This will allow a long window of opportunity for disease prevention.
Date proposal received: 
Friday, 21 January, 2022
Date proposal approved: 
Monday, 24 January, 2022
Epidemiology, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Allergy, Eating disorders - anorexia, bulimia, Eczema, Epilepsy, Fertility/infertility, Gastrointestinal, Hypertension, Incontinence, Infection, Learning difficulty, Mental health, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Obesity, Pain, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Respiratory - asthma, Sexually transmitted diseases, chlamydia, gonorrhoea, Speech/language problem, Bone disorders - arthritis, osteoporosis, Developmental disorders - autism, Cancer, Chronic fatigue, Cognitive impairment, Congenital abnormalities, Diabetes, GWAS, Metabolomics, NMR, Proteomics, RNA, Statistical methods, Genetic epidemiology, Genome wide association study, Mendelian randomisation, Statistical methods