No Evidence that 2D:4D is Related to the Number of CAG Repeats in the Androgen Receptor Gene

Abstract

The length ratio of the second to the fourth digit (2D:4D) is a putative marker of prenatal testosterone (T) effects. The number of CAG repeats (CAGn) in the AR gene is negatively correlated with T sensitivity in vitro. Results regarding the relationship between 2D:4D and CAGn are mixed but have featured prominently in arguments for and against the validity of 2D:4D. Here, I present random-effects meta-analyses on 14 relevant samples with altogether 1904 subjects. Results were homogeneous across studies. Even liberal estimates (upper limit of the 95% CI) were close to zero and therefore suggested no substantial relationship of CAGn with either right-hand 2D:4D, left-hand 2D:4D, or the difference between the two. However, closer analysis of the effects of CAGn on T dependent gene activation in vitro and of relationships between CAGn and T dependent phenotypic characteristics suggest that normal variability of CAGn has mostly no, very small, or inconsistent effects. Therefore, the lack of a clear association between CAGn and 2D:4D has no negative implications for the latter's validity as a marker of prenatal T effects.

Keywords: 2D:4D; AR gene; CAG repeats; meta-analysis; testosterone.

Figure 1

Fictitious example of in vitro study into the effect of CAGn on target gene activity. Example for regression of the activity of a testosterone regulated target gene on CAGn in in vitro studies (cf. Table 1). ARs with CAGn of 0, 15, 18, 21, 24, or 27 are used either with testosterone (gray bars) or without testosterone (black bars). Target gene activity observed at CAGn most typical in humans (21) is set to 100%. Then the regression slope (dashed line, −2.3%) is calculated to describe target gene activity as a function of CAGn. In cases like the present, where CAGn outside the human range produce a deviation from linearity (here 0 CAGn), the regression slope was calculated only for those CAGn that showed a linear function.