FIG. 2.

Conceptual hypotheses of structure of linkage of genes (G) with aging-related traits (D). (A) The basic concept, known as the common disease–common variants (CDCV) hypothesis, adopts linear structure when few genes can influence a given trait. (B) The CDCV hypothesis becomes discouraging whereas the risk hypothesis is strengthened; the risk hypothesis emphasizes the concept of polygenicity (many genes–one phenotype). (C) Recognition of fundamental role of pleiotropy (one gene–multiple phenotypes) in aging-related traits implies that the pleiotropy concept should complement the concept of polygenicity. (D) Superposition of these two concepts constitutes qualitative transition from the linear structure to the net structure formalized as the diseasome. (E) Recognition of the dynamic concept of genetic susceptibility to aging-related traits (Fig 1B) leads to the concept of the dynamic diseasome.