The Effect of Ancestry and Genetic Variation on Lung Function Predictions: What Is "Normal" Lung Function in Diverse Human Populations?

Lung function measures are an invaluable screening test for respiratory health and have been associated with the morbidity and mortality related to different airway disease as well as all-cause mortality. Currently, reference values for spirometric measurements are obtained using equations derived from individual ethnic or racial groups. The rapid expansion of more racially and ethnically diverse populations will challenge current race-based lung function reference equations. Recent international general population studies and ancestry-based genetic studies have found that ancestry and genetic variation are determinants of lung function and have suggested a role for genetic ancestry or gene variants in future lung function reference equations. In this review, we discuss the potential limitations of current lung function reference equations in a global society which is becoming more ethnically, racially, and, thus, genetically diverse. We also focus on how an individual's ancestral background or genetic profile could provide the basis for more accurate, personalized predictions of an individual's baseline lung function.