Principal Investigator: Professor Gianpiero Cavalleri
Royal College of Surgeons in IrelandTags: 35124, Ancestry, Creatinine, epilepsy, kidney, psychosis, skin
Many small genetic changes can contribute to a given human trait. We will create a score based on thousands of genetic variants that have been previously associated with skin cancer, kidney function and psychosis for each individual in the proposed datasets and tested as a predictor of these traits. The effect sizes will then be compared to our screened populations to see if they are significantly different. We will compare these risk scores in the following screened populations: – Skin cancer – we will compare the risk score calculated in the UK Biobank to people exposed to immunosuppressant drug treatment as part of a post-transplant treatment plan. This will allow us to see if the risk score is predictive of skin cancer in those who are exposed to these kinds of drugs (which are known to increase skin cancer risk) or predictive of skin cancer in the general population. – Kidney function – we will compare the risk score calculated in the UK Biobank to people who have undergone a kidney transplant to see if the risk score is predictive of how well the transplanted kidney functions or if it can predict kidney function in non-transplanted individuals also. – Psychosis – we will compare risk scores calculated in the UK Biobank to individuals who have been exposed to specific epilepsy medications and those who have epilepsy. This will allow us to find out if these risk scores can predict psychosis in general or if it can only predict psychosis in individuals with epilepsy. This research aims to improve the safe and effective treatment of illness by creating risk scores that can identify patients at risk of treatment complications. We will also compare the genomes of individuals with Irish ancestry from specific regions in Ireland, and individuals from Britain and compare which regions in Britain share more ancestry with regions in Ireland). Investigating the genetic similarities and shared structure between British and Irish populations will aid in the design of genetic studies in particular in rare genetic marker discovery. Our research also aims to identify genetic markers that can be used to aid the diagnosis of disease (specifically in the development of epilepsy). We expect the completion of these aims will take 24 months.
Our specific aims are to use UK Biobank data to determine:
- The predictive ability of polygenic risk scores (PRS) of non-melanoma skin cancer, specifically in a population exposed to immunosuppressants (as used for organ transplantation).
- The predictive ability of PRS on kidney function, in the setting of kidney transplantation.
- The predictive ability of PRS on acute psychosis (e.g. drug-induced) and psychosis as a co-morbidity of other diseases.
- The role of genetic variation in the development of epilepsy.
- The genetic links between Ireland and Britain, and ask what regions in Britain share more genetic affinity with Ireland than others.
- Investigate the role of PRS of circadian rhythm on transplant-related outcomes.
– For this project, we wish to test a PRS of circadian rhythm, calculated using results data from a previous GWAS of PRS (Hu et al. 2016) as a predictor of chronotype on the UK Biobank. First, we wish to see if this risk score can predict chronotype using the UK Biobank data – we have requested additional data on shift work to include as a covariate in this analysis. If the PRS is a predictor of chronotype in the UK Biobank, we will then apply it in our transplant cohort (the UK and Ireland Renal Transplant consortium) as a predictor of transplant outcome.
- Investigate the genetics of the causes of death in a population of deceased kidney-transplant donors utilizing the UK Biobank as a control dataset.
– For this project, we wish to use the UK Biobank genotype data to act as a healthy control population for a GWAS of cause of death. For this, we will combine the UK Biobank data with a cohort of deceased kidney transplant donors from the UK and Ireland Renal Transplant consortium. We will then carry out a number of GWAS investigating the different causes of death in our deceased-donor cohort using the UK Biobank as controls.
Last updated Feb 2, 2019