The second to fourth digit ratio and variation in the androgen receptor gene

The second to fourth digit ratio (2D:4D) is sexually dimorphic, with lower mean values in males compared to females. It has been suggested that the sex difference in 2D:4D is determined prenatally, 2D:4D is negatively related to prenatal testosterone and positively to prenatal oestrogen, and that 2D...

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Published in:Evolution and human behavior Vol. 24; no. 6; pp. 399 - 405
Main Authors: Manning, John T., Bundred, Peter E., Newton, Darren J., Flanagan, Brian F.
Format: Journal Article
Language:English
Published: Elsevier Inc 01-11-2003
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Abstract The second to fourth digit ratio (2D:4D) is sexually dimorphic, with lower mean values in males compared to females. It has been suggested that the sex difference in 2D:4D is determined prenatally, 2D:4D is negatively related to prenatal testosterone and positively to prenatal oestrogen, and that 2D:4D is a marker for levels of sex steroids during brain organisation. There is growing evidence that many sex-dependent behaviours are correlated with 2D:4D. However, there is no direct evidence for an effect of prenatal sex steroids on the digit ratio. The response to prenatal testosterone is dependent on the amount produced and the foetal sensitivity to the hormone. Variation in the X-linked androgen receptor gene (AR) determines sensitivity to testosterone. Alleles of AR with low numbers of CAG triplets respond to testosterone with high transactivational activity, while high numbers of CAG's are associated with increased insensitivity to testosterone. We show in a sample of 50 men (49 Caucasian subjects, 1 Caucasian/Chinese subject) that 2D:4D is a phenotypic correlate of AR structure. Right-hand 2D:4D was positively correlated with CAG number and individuals with low 2D:4D in their right hand compared to left hand had AR alleles with low CAG numbers. We discuss the implications of our findings for our understanding of the aetiology of 2D:4D, its relationships with sex-dependent behaviours, and the evolutionary implications of variation in 2D:4D and AR.
AbstractList The second to fourth digit ratio (2D:4D) is sexually dimorphic, with lower mean values in males compared to females. It has been suggested that the sex difference in 2D:4D is determined prenatally, 2D:4D is negatively related to prenatal testosterone and positively to prenatal oestrogen, and that 2D:4D is a marker for levels of sex steroids during brain organisation. There is growing evidence that many sex-dependent behaviours are correlated with 2D:4D. However, there is no direct evidence for an effect of prenatal sex steroids on the digit ratio. The response to prenatal testosterone is dependent on the amount produced and the foetal sensitivity to the hormone. Variation in the X-linked androgen receptor gene (AR) determines sensitivity to testosterone. Alleles of AR with low numbers of CAG triplets respond to testosterone with high transactivational activity, while high numbers of CAG's are associated with increased insensitivity to testosterone. We show in a sample of 50 men (49 Caucasian subjects, 1 Caucasian/Chinese subject) that 2D:4D is a phenotypic correlate of AR structure. Right-hand 2D:4D was positively correlated with CAG number and individuals with low 2D:4D in their right hand compared to left hand had AR alleles with low CAG numbers. We discuss the implications of our findings for our understanding of the aetiology of 2D:4D, its relationships with sex-dependent behaviours, and the evolutionary implications of variation in 2D:4D and AR.
Author Bundred, Peter E.
Newton, Darren J.
Manning, John T.
Flanagan, Brian F.
Author_xml – sequence: 1
  givenname: John T.
  surname: Manning
  fullname: Manning, John T.
  email: jtmanning@uclan.ac.uk
  organization: Department of Psychology, University of Central Lancashire, Preston, PR1 2HE, UK
– sequence: 2
  givenname: Peter E.
  surname: Bundred
  fullname: Bundred, Peter E.
  organization: Department of Primary Care, University of Liverpool, Liverpool L69 3BX, UK
– sequence: 3
  givenname: Darren J.
  surname: Newton
  fullname: Newton, Darren J.
  organization: Department of Immunology, University of Liverpool, Liverpool L69 3BX, UK
– sequence: 4
  givenname: Brian F.
  surname: Flanagan
  fullname: Flanagan, Brian F.
  organization: Department of Immunology, University of Liverpool, Liverpool L69 3BX, UK
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Snippet The second to fourth digit ratio (2D:4D) is sexually dimorphic, with lower mean values in males compared to females. It has been suggested that the sex...
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StartPage 399
SubjectTerms 2D:4D
Androgen receptor
Ethology
Genetics
Human behaviour
Human evolution
Sociobiology
Title The second to fourth digit ratio and variation in the androgen receptor gene
URI https://dx.doi.org/10.1016/S1090-5138(03)00052-7
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