La génomique de l'ostéoporose et de la vitamine D : des corrélations à la causalité jusqu'à l'application clinique


Brent Richards

Institut Lady Davis de recherches médicales de l'Hôpital général juif


Domaine :  génétique humaine

Programme chercheurs-boursiers-cliniciens  - Senior

Concours 2017-2018

My program focuses on two inter-related questions. First, what are the genetic determinants of osteoporosis and one of its key risk factors, vitamin D insufficiency? And second, how can this information be used to improve clinical care?

We will address the first question through genome-wide association studies (GWAS), whole genome sequencing and follow-up functional genomics and animal studies. To examine the second question, we will use genetics to identify high-yield drug targets for osteoporosis and to test the causality of vitamin D insufficiency in osteoporotic fractures.

Osteoporotic fractures affect one quarter of Canadians and cost $2.3 billion annually. Fractures are due to decreased bone quantity (clinically measured through bone mineral density [BMD]) and bone quality. Current therapies increase BMD, yet few are safe, effective and affordable and none act through BMD-independent pathways. Human genetics provides efficient tools to identify drug targets for disease in general and osteoporosis in particular. We will therefore use human genetics to identify BMD-independent drug targets for osteoporosis.

Vitamin D insufficiency affects one half of Canadians and is associated with lowered BMD, yet its effect on fracture risk is not clear. While vitamin D insufficiency has been variably associated with fracture, such associations may be simply markers for other factors, since vitamin D is strongly correlated with adiposity and healthy lifestyles. However, if vitamin D were causal, this would be of public health importance, since it can be measured and corrected. We will therefore use a genetic epidemiology method called Mendelian randomization to test the causality of vitamin D in osteoporotic fracture.