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.

Digit ratio (2D:4D) and salivary testosterone, oestradiol and cortisol levels under challenge: Evidence for prenatal effects on adult endocrine responses

“…Similarly, more direct evidence shows that 2D:4D strongly predicts the effects of T administration on empathy and cooperation in women [32,33]. These findings suggest that 2D:4D is a putative marker for sensitivity to T, although attempts to show that 2D:4D correlates with the androgen receptor gene have been inconclusive [34].…”

Revisiting the relationships of 2D:4D with androgen receptor (AR) gene and current testosterone levels: Replication study and meta‐analyses

“…For a long time, the relationship between AR (CAG)n and the ratio has been used as the index in assessing the effect of fetal testosterone level on 2D:4D (Manning, Bundred, Newton, & Flanagan, ). Unfortunately, two early meta‐analyses indicated that AR (CAG)n is not significantly associated with the ratio (Hönekopp, ; Voracek, ). However, the conclusion from the meta‐analyses were not supported by the subsequent studies with new samples (Durdiaková et al, ; Durdiaková, Celec, Laznibatova, Minarik, & Ostatnikova, ; Warrington et al, ).…”

No Sexual Dimorphism Detected in Digit Ratios of the Fire Salamander (Salamandra salamandra)

“…The skeletogenic genes, some 20 in number, have multiple additional functions, which include the morphogenesis of the reproductive organs and the brain (Zheng and Cohn, ; Lawrance‐Owen et al, ). However, no firm links between variants of the AR and (postnatal) 2D:4D have been identified in humans (Hönekopp, ; Voracek, ) or zebra finches (Forstmeier et al, ), although a relationship with the ER‐α in zebra finches has been shown (Forstmeier et al, ). In humans, van Honk et al have reported that 2D:4D strongly moderates the influence of experimentally administered exogenous testosterone on empathy (van Honk et al, ), co‐operation (van Honk et al, ), and moral judgments (Montoya et al, ) in women.…”