Twins and the mystery of missing heritability: the contribution of gene-environment interactions.

Since 2006, the advent of increasingly larger genome-wide association studies and their meta-analyses have led to numerous, replicated findings of genetic polymorphisms associated with many diseases and traits. Early studies suggested that the identified loci generally accounted for a small fraction of the genetic variance estimated from twin and family studies. This led to the concept of 'missing heritability'. Here, the progress in accounting for a greater proportion of the variance is reviewed. In particular, gene-environment interactions can, for some traits and in certain circumstances, explain part of this missing heritability.