Cutting the fat: advances and challenges in sleep apnoea genetics

Obstructive sleep apnoea (OSA), characterised by recurrent upper airway obstruction, intermittent hypoxia and fragmented sleep, affects >15% of the adult population, with prevalence increasing markedly with advancing age and age-related cardiometabolic and pulmonary disorders [1]. Causal associations between OSA and hypertension, coronary heart disease, diabetes, heart failure, atrial fibrillation, stroke and mortality are suggested by numerous large prospective studies [2], raising the possibility that effective treatment of OSA might provide a novel strategy for primary and secondary prevention of cardiometabolic disease. However, randomised controlled trials have not yet produced evidence that use of a device for splinting the airway (i.e. continuous positive pressure) improves clinical cardiovascular disease. Multiple potential reasons for these disappointing results have been suggested, ranging from inadequate use of continuous positive pressure due to device intolerance, to exclusion of individuals from the trials who are most susceptible to OSA-related adverse outcomes. It is increasingly evident that there is a need to better identify OSA phenotypes that predict individuals at highest risk for developing chronic disease, as well as the underlying OSA disease mechanisms most amenable to targeted interventions.