Abstract
Men and women differ statistically in the relative lengths of their index and ring fingers; and the ratio of these lengths has been used as a biomarker for prenatal testosterone. The ratio has been correlated with a wide range of traits and conditions including prostate cancer, obesity, autism, ADHD, and sexual orientation. In a genome-wide association study of 979 healthy adults, we find that digit ratio is strongly associated with variation upstream of SMOC1 (rs4902759: P = 1.41 × 10−8) and a meta-analysis of this and an independent study shows a probability of P = 1.5 × 10−11. The protein encoded by SMOC1 has recently been shown to play a critical role in limb development; its expression in prostate tissue is dependent on sex hormones, and it has been implicated in the sexually dimorphic development of the gonads. We put forward the hypothesis that SMOC1 provides a link between prenatal hormone exposure and digit ratio.
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Acknowledgments
This work was supported by the Gatsby Charitable Foundation [GAT2903]. We are grateful to Horace Barlow, Roger Freedman, Graeme Mitchison and Richard Durbin for their role in the initiation of the PERGENIC project, to Julien Bauer, Emily Clemente and Kerry Cliffe of Cambridge Genomic Services for their valuable help, and to Julian Sale for comments on the manuscript.
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Lawrance-Owen, A.J., Bargary, G., Bosten, J.M. et al. Genetic association suggests that SMOC1 mediates between prenatal sex hormones and digit ratio. Hum Genet 132, 415–421 (2013). https://doi.org/10.1007/s00439-012-1259-y
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DOI: https://doi.org/10.1007/s00439-012-1259-y