Heritability is defined as the ratio of the genetic variance over the total variance of a trait [1], and can differ between the sexes for multiple reasons. Different genes can be expressed in men and women, but even when the same genes are expressed in both sexes their relative importance can differ, and the environmental variance can vary, thereby also changing the ratio of genetic over total variance. In a classical paper from 1978, Eaves et al suggested that the key to detection of sex by genotype interactions lies with opposite-sex twin pairs who should be comparable in their similarity with dizygotic same-sex (DZss) twin pairs if a similar mechanism is accounting for the variation in the trait in males and females [2]. To cite Eaves and colleagues: “Many twin studies in the past have deliberately excluded unlike-sex twins, presumably out of a mistaken belief that concentrating on like-sex pairs ‘controls’ for the effect of sex. In reality, exactly the reverse is true. Omission of unlike-sex pairs removes the most important tool for the early identification of sex-dependent mechanisms of determination.”
