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MRC DTP 4 Year PhD Programme: Identifying genetic factors contributing to knee pain and knee osteoarthritis among people with diabetes


About This PhD Project

Project Description


This project is offered as part of the University of Dundee 4-year MRC DTP Programme “Quantitative and Interdisciplinary approaches to biomedical science”. This PhD programme brings together leading experts from the School of Life Sciences (SLS), the School of Medicine (SoM) and the School of Science and Engineering (SSE) to train the next generation of scientists at the forefront of international science. The outstanding biomedical research at the University of Dundee was recognised by its very high rankings in REF 2014, with Dundee rated as the top University for Biological Sciences in the UK. A wide range of projects are available within this programme crossing exceptional strengths in four key areas: Infection and Disease; Responses to Cellular Stresses; Development, Stem Cells and Neurobiology; and Big Data and Translation. All students on this programme will receive training in computational biology, mathematical biology and statistics to equip with the quantitative skills in tackling complex biological questions. In the 1st year, students will carry out 3 rotation projects prior to selection of the final PhD project.

Diabetes patients are more likely to have osteoarthritis than non-diabetic subjects and many patients with diabetes suffer knee pain.[1] This knee pain may be caused or aggravated by excess weight, which is a common problem in those withtype 2 diabetes. [2] We hypothesise that specific genetic factors play a role in knee pain and knee osteoarthritis in people with diabetes. These genetic factors may be directly or indirectly related, for example due to raised BMI, or neuropathy, or may be independent.We have collected, or have access to the genetic information of samples from approximately 40,000 people with diabetes from the GoDARTS (N=10,000) and the UK Biobank cohorts (N=30,000). We estimate 90% of them have type 2 diabetes. We plan to perform a survey study to collect the phenotype information of knee pain and knee osteoarthritis among the participants of the GoDARTS cohort while the phenotype informationof the UK Biobank cohorthas been already obtained. Then, we will perform relevant genome-wide association study(GWAS)to identify the genes for knee pain and knee osteoarthritis among diabetes patients.This will be the first GWAS on knee pain and knee osteoarthritis specifically in people with diabetes to search for related genes.The student will perform a literature review of knee pain and knee osteoarthritis firstly and then he will learn to use GWAS related software to to perform the analysis, and to understand, explore and explain the genetic results. He will also participate in the survey design and communicate with the Health Informatic Centre within the School of Medicine which will perform the survey.



References

References:

1.Piva SR, et al. Links between osteoarthritis and diabetes: implications for management from a physical activity perspective.Clin Geriatr Med. 2015;31:67-87.

2.Rogers MW, et al. The association of BMI and knee pain among persons with radiographic knee osteoarthritis: A cross-sectional study. BMC Musculoskelet Disord. 2008;9:163.

Recent work from the lab can be found in the following references:

1. Meng W et al. Genome-wide association study of knee pain identifies associations with GDF5 and COL27A1 in UK Biobank.Commun Biol. 2019 Aug 28;2:321.

2. Meng et al. Genetic correlations between pain phenotypes and depression and neuroticism. European Journal of Human Genetics. 2019 Sept accepted.

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