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2D:4D ratios in the first 2 years of life: Stability and relation to testosterone exposure and sensitivity
Rebecca C Knickmeyer1, Sandra Woolson, Robert M Hamer
1Department of Psychiatry, University of North Carolina, CB 7160, Chapel Hill, NC 27599-7160, USA. rebecca_knickmeyer@med.unc.edu
Insights
Digit ratio (2D:4D) in infants shows high variability and small sex differences, questioning its use as a prenatal testosterone marker. Neonatal testosterone and androgen receptor gene interactions may influence digit ratio in males.
Area of Science:
- Developmental biology
- Endocrinology
- Anthropometry
Background:
- The 2nd to 4th digit ratio (2D:4D) is a proposed marker for prenatal androgen exposure.
- Its development in infancy and relation to neonatal testosterone levels remain understudied.
Purpose of the Study:
- To investigate the development of 2D:4D in children aged 0-2 years.
- To examine the association between 2D:4D, neonatal testosterone, and androgen receptor (AR) gene CAG repeat length.
Main Methods:
- Collected 2D:4D ratios from 364 children (0-2 years).
- Measured salivary testosterone in 236 infants at 3 months.
- Genotyped 259 children for AR CAG repeat polymorphism.
Main Results:
- 2D:4D showed significant age-related variability and minimal, inconsistent sex differences in infancy.
- In males, the interaction of salivary testosterone and AR CAG repeat length predicted 2D:4D at 12 and 24 months, and changes in left-hand 2D:4D from 2 weeks to 12 months.
- No significant associations were found in females or when testosterone and CAG repeats were analyzed independently.
Conclusions:
- Infant 2D:4D is not a reliable proxy for prenatal testosterone exposure.
- Neonatal testosterone and AR genotype may influence digit ratio development in males, suggesting a potential link to later 2D:4D.
- Findings impact the interpretation of studies using 2D:4D as a prenatal androgen exposure biomarker.
Abstract:
The relative lengths of the 2nd and 4th digits (2D:4D) may provide an easily measurable and stable anthropometric index of prenatal androgen exposure, but no study has examined the development of 2D:4D in infancy and the potential impact of neonatal testosterone levels. We collected 2D:4D ratios from 364 children between 0 and 2 years of age. Saliva samples were collected from 236 of these children 3 months after birth and analyzed for testosterone. In addition, 259 children provided DNA samples which were genotyped for the CAG repeat polymorphism in the androgen receptor. There was substantial variability across age in 2D:4D. Sex differences were small compared to adults and did not consistently reach statistical significance. This suggests that 2D:4D may not function well as a proxy measure of prenatal testosterone exposure in infancy. In addition, the interaction of salivary T and CAG repeats predicted right hand digit ratio at 12 months and left hand digit ratio at 12 months and 24 months in males. The interaction of salivary testosterone and CAG repeat length also predicted change in left hand 2D:4D from 2 weeks to 12 months in males. This suggests that 2D:4D in adults may reflect, in part, neonatal testosterone exposure. No significant relationships were observed within females. No significant relationships were observed when salivary testosterone and CAG repeats were examined independent of each other. Results have important implications for the design and interpretation of studies which use 2D:4D as a proxy measure of prenatal testosterone exposure.
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