Genetic Association Suggests That SMOC1 Mediates Between Prenatal Sex Hormones and Digit Ratio

Overview

Journal Hum Genet

Specialty Genetics

Date 2012 Dec 25

PMID 23263445

Citations 14

Authors

Adam J Lawrance-Owen

Gary Bargary

Jenny M Bosten

Patrick T Goodbourn

Ruth E Hogg

J D Mollon

Affiliations

Soon will be listed here.

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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References

Kondo T, Zakany J, Innis J, Duboule D . Of fingers, toes and penises. Nature. 1997; 390(6655):29. DOI: 10.1038/36234. View

Nelson E, Rolian C, Cashmore L, Shultz S . Digit ratios predict polygyny in early apes, Ardipithecus, Neanderthals and early modern humans but not in Australopithecus. Proc Biol Sci. 2010; 278(1711):1556-63. PMC: 3081742. DOI: 10.1098/rspb.2010.1740. View

Goodbourn P, Bosten J, Hogg R, Bargary G, Lawrance-Owen A, Mollon J . Do different 'magnocellular tasks' probe the same neural substrate?. Proc Biol Sci. 2012; 279(1745):4263-71. PMC: 3441081. DOI: 10.1098/rspb.2012.1430. View

Howie B, Donnelly P, Marchini J . A flexible and accurate genotype imputation method for the next generation of genome-wide association studies. PLoS Genet. 2009; 5(6):e1000529. PMC: 2689936. DOI: 10.1371/journal.pgen.1000529. View

A Rahman A, Lophatananon A, Stewart-Brown S, Harriss D, Anderson J, Parker T . Hand pattern indicates prostate cancer risk. Br J Cancer. 2010; 104(1):175-7. PMC: 3039824. DOI: 10.1038/sj.bjc.6605986. View

Klump K, Gobrogge K, Perkins P, Thorne D, Sisk C, Marc Breedlove S . Preliminary evidence that gonadal hormones organize and activate disordered eating. Psychol Med. 2005; 36(4):539-46. DOI: 10.1017/S0033291705006653. View

Bradshaw A . Diverse biological functions of the SPARC family of proteins. Int J Biochem Cell Biol. 2012; 44(3):480-8. PMC: 3312742. DOI: 10.1016/j.biocel.2011.12.021. View

Howie B, Marchini J, Stephens M . Genotype imputation with thousands of genomes. G3 (Bethesda). 2012; 1(6):457-70. PMC: 3276165. DOI: 10.1534/g3.111.001198. View

Fink B, Manning J, Neave N . The 2nd-4th digit ratio (2D:4D) and neck circumference: implications for risk factors in coronary heart disease. Int J Obes (Lond). 2005; 30(4):711-4. DOI: 10.1038/sj.ijo.0803154. View

10.

Coates J, Gurnell M, Rustichini A . Second-to-fourth digit ratio predicts success among high-frequency financial traders. Proc Natl Acad Sci U S A. 2009; 106(2):623-8. PMC: 2626753. DOI: 10.1073/pnas.0810907106. View

11.

Yuan X, Lu M, Li T, Balk S . SRY interacts with and negatively regulates androgen receptor transcriptional activity. J Biol Chem. 2001; 276(49):46647-54. DOI: 10.1074/jbc.M108404200. View

12.

Peters M, Manning J, Reimers S . The effects of sex, sexual orientation, and digit ratio (2D:4D) on mental rotation performance. Arch Sex Behav. 2007; 36(2):251-60. DOI: 10.1007/s10508-006-9166-8. View

13.

Talarovicova A, Krskova L, Blazekova J . Testosterone enhancement during pregnancy influences the 2D:4D ratio and open field motor activity of rat siblings in adulthood. Horm Behav. 2008; 55(1):235-9. DOI: 10.1016/j.yhbeh.2008.10.010. View

14.

Rainger J, van Beusekom E, Ramsay J, McKie L, Al-Gazali L, Pallotta R . Loss of the BMP antagonist, SMOC-1, causes Ophthalmo-acromelic (Waardenburg Anophthalmia) syndrome in humans and mice. PLoS Genet. 2011; 7(7):e1002114. PMC: 3131273. DOI: 10.1371/journal.pgen.1002114. View

15.

Forstmeier W, Mueller J, Kempenaers B . A polymorphism in the oestrogen receptor gene explains covariance between digit ratio and mating behaviour. Proc Biol Sci. 2010; 277(1698):3353-61. PMC: 2981936. DOI: 10.1098/rspb.2010.1007. View

16.

Abecasis G, Altshuler D, Auton A, Brooks L, Durbin R, Gibbs R . A map of human genome variation from population-scale sequencing. Nature. 2010; 467(7319):1061-73. PMC: 3042601. DOI: 10.1038/nature09534. View

17.

Choi I, Kim K, Jung H, Yoon S, Kim S, Kim T . Second to fourth digit ratio: a predictor of adult penile length. Asian J Androl. 2011; 13(5):710-4. PMC: 3739592. DOI: 10.1038/aja.2011.75. View

18.

Love H, Booton S, Boone B, Breyer J, Koyama T, Revelo M . Androgen regulated genes in human prostate xenografts in mice: relation to BPH and prostate cancer. PLoS One. 2009; 4(12):e8384. PMC: 2793011. DOI: 10.1371/journal.pone.0008384. View

19.

Berenbaum S, Bryk K, Nowak N, Quigley C, Moffat S . Fingers as a marker of prenatal androgen exposure. Endocrinology. 2009; 150(11):5119-24. PMC: 2775980. DOI: 10.1210/en.2009-0774. View

20.

Grimbos T, Dawood K, Burriss R, Zucker K, Puts D . Sexual orientation and the second to fourth finger length ratio: a meta-analysis in men and women. Behav Neurosci. 2010; 124(2):278-87. DOI: 10.1037/a0018764. View