Fig. 1.

Complex landscape for predicting allelic variants that impact health. A. Single variant example. Even after delineating a variant that projects a high risk for developing a disease, outcomes can be very different where one individual may succumb to a deleterious variant while another individual with the same variant may remain healthy and never develop disease – the concept of penetrance. B. Multi/polygenic example. Many traits are influenced by a combination of allelic variants and therefore are more challenging to directly map to a trait. In both scenarios, external factors (lifestyle, environment, and the microbiome) frequently are involved in how the effects of these variants play out and whether an individual remains healthy or develops disease.