in Framingham). Thus, not only there may be a difference in the identity of specific genetic determinants for each trait46, but rather the genetic architecture may be distinct for each trait, with more modest effects, fewer loci, rarer variants or a stronger environmental modification underlying HOMA-IR. In addition, HOMA-IR (which is composed of fasting values) is an imperfect estimate of global insulin resistance, as it addresses mostly hepatic sensitivity to insulin and is partially affected by β-cell function: its heritability is lower than insulin sensitivity derived from the minimal model47. Exploration of gene × environment interactions and analysis of datasets that include 2-hour glucose and insulin values may reveal other genetic factors that increase insulin resistance in humans29.
