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Approved research

Discovery of skeletal and non-skeletal phenotypic characteristics in the UK population using genetic variants identified from musculoskeletal cases in the 100,000 (100K) Genomes Project.

Principal Investigator: Dr Alistair Pagnamenta
Approved Research ID: 56533
Approval date: January 15th 2020

Lay summary

This application is part of a larger project to find the disease-causing genes in patients with rare bone diseases. There are almost 500 types of rare inherited bone disorders. These disorders are caused by changes in genes that stop bones growing normally. For a third of rare bone diseases, we do not know which gene is involved. The NHS 100K Genomes Project has been set up study the genes of patients with rare diseases ,to help provide a diagnosis for these families. Once the gene causing the disease is found, researchers can use this new knowledge to develop better tests and treatments for the rare disease but also for patients with commoner bone conditions such as osteoporosis and osteoarthritis, a major public health benefit. Already, two treatments for osteoporosis, which affects 3.5 million people in the UK, were found through studying a rare bone disease that affects fewer 1:100,000 people. In the 100K Genomes project, we usually find differences in many genes that could be causing the patient's rare bone disease. Researchers then have to look for additional clues to help select the most likely gene(s) to take forward into more complex experiments. While big changes to the gene often cause major problems for patients, smaller changes in genes can cause smaller differences in otherwise healthy patients. The aim of this application is to take the list of genes found in the 100K project for people with rare bone diseases and see if in UK Biobank, small differences in these genes are linked to differences in other bone characteristics such as height, frequency of fractures, dental history, bone density or with effects on other body systems such as hearing. This project will run for five years.