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.