In our ageing population, the prevalence of many common diseases is increasing and their burden threatens our societies. For instance, cardiovascular diseases remain the leading cause of mortality worldwide. In Canada, more than 1.6 million individuals have heart diseases and direct costs for treating cardiovascular diseases are $7.4 billion per year, the highest for a disease. Hypertension is the most common cardiovascular disease in the world (1.13 billion people) and account for 13 per cent of annual deaths worldwide. Finally, dementia affects 50 million people worldwide and this number is expected to triple by 2050 at an estimated cost for the societies of $4 trillion. These three examples highlight the burden that such diseases represent in our societies, and the need to improve their prognostic, diagnostic and treatment. Precision medicine aims to identify the root causes of diseases in order to tailor prediction, prevention and treatment to each individual. One strategy to achieve this aim is to integrate into clinical care information hidden in the DNA of each person. Whole-genome DNA sequencing is now a robust technique that can reliably read a person’s genome, that is, the information contained in a person’s DNA. Several international efforts are currently ongoing in order to document genetic variation in different human populations. Our project – the GenoRef-Q Initiative – will sequence the genome of 1900 participants recruited in CARTaGENE, the population-based cohort of the Province of Quebec. This resource will enable multiple precision medicine-related activities and set the stage for future projects led by the new generation of scientists. For example, the GenoRef-Q Initiative will create a comprehensive catalogue of genetic variants found in the population of Quebec, a formidable tool for clinical geneticists and other clinicians to interpret the results of genetic testing and to pinpoint the cause of various genetic diseases. The sequence information will also be useful to decipher existing genetic data and to prioritize further development of more specific drug targets. The GenoRef-Q Initiative will create opportunities for researchers in Quebec, in Canada, and internationally that will foster research in human genetics and precision medicine. This, in turn, will lead to a better understanding of genetic risk in Canadian populations. As such, it is perfectly aligned with the priorities of multiple universities and research centers, as well as the provincial and federal governments.