Medland, Sarah E., Zayats, Tetyana, Glaser, Beate, Nyholt, Dale R., Gordon, Scott D., Wright, Margaret J., Montgomery, Grant W., Campbell, Megan J., Henders, Anjali K., Timpson, Nicholas J., Peltonen, Leena, Wolke, Dieter, Ring, Susan M., Deloukas, Panos, Martin, Nicholas G., Smith, George Davey and Evans, David M.. (2010) A variant in LIN28B is associated with 2D:4D finger-length ratio, a putative retrospective biomarker of prenatal testosterone exposure. American Journal of Human Genetics, Vol.86 (No.4). pp. 519-525. ISSN 0002-9297

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Abstract

The ratio of the lengths of an individual's second to fourth digit (2D:4D) is commonly used as a noninvasive retrospective biomarker for prenatal androgen exposure. In order to identify the genetic determinants of 2D:4D, we applied a genome-wide association approach to 1507 11-year-old children from the Avon Longitudinal Study of Parents and Children (ALSPAC) in whom 2D:4D ratio had been measured, as well as a sample of 1382 12- to 16-year-olds from the Brisbane Adolescent Twin Study. A meta-analysis of the two scans identified a single variant in the LIN28B gene that was strongly associated with 2D:4D (rs314277: p = 4.1 108) and was subsequently independently replicated in an additional 3659 children from the ALSPAC cohort (p = 1.53 106). The minor allele of the rs314277 variant has previously been linked to increased height and delayed age at menarche, but in our study it was associated with increased 2D:4D in the direction opposite to that of previous reports on the correlation between 2D:4D and age at menarche. Our findings call into question the validity of 2D:4D as a simplistic retrospective biomarker for prenatal testosterone exposure.

Item Type:	Journal Article
Subjects:	Q Science > QP Physiology R Medicine > RG Gynecology and obstetrics
Divisions:	Faculty of Science > Psychology
Library of Congress Subject Headings (LCSH):	Fingers -- Size, Androgens, Maternal-fetal exchange, Human genetics, Biochemical markers
Journal or Publication Title:	American Journal of Human Genetics
Publisher:	Elsevier
ISSN:	0002-9297
Date:	9 April 2010
Volume:	Vol.86
Number:	No.4
Page Range:	pp. 519-525
Identification Number:	10.1016/j.ajhg.2010.02.017
Status:	Peer Reviewed
Access rights to Published version:	Open Access
Funder:	Medical Research Council (Great Britain) (MRC), Wellcome Trust (London, England), University of Bristol, National Health and Medical Research Council (Australia) (NHMRC), Australian Research Council (ARC), Nederlandse Organisatie voor Wetenschappelijk Onderzoek [Netherlands Organisation for Scientific Research] (NWO)
Grant number:	90600705(MRC), 0800582(MRC), 241944(NHMRC), 339462(NHMRC), 389927(NHMRC), 389875(NHMRC), 389891(NHMRC), 389892(NHMRC), 389938(NHMRC), 443036(NHMRC), 442915(NHMRC), 442981(NHMRC), 496739(NHMRC), 552485(NHMRC), 552498(NHMRC), 480-05-003(NWO)
References:	1. Phelps VR (1952) Relative finger lengths as a sex-influenced trait in man. Amer J Hum Genet 4:72-89 2. Ecker A (1875) Einige Bemerkungen über einen schwankenden charakter in der hand des menschen [Some remarks on a varying property of the human hand]. Archiv fur Anthroplogie 8:67-74 3 Wilson G.D. (1983) Finger length as an index of assertiveness in women. Personal. Individ. Diff. 4:111-112 4. Manning JT (2002) Digit Ratio:A pointer to fertility, behavior, and health. Rutgers University Press, New Brunswick 5. Manning JT, Scutt D, Wilson J, Lewis-Jones DI (1998) The ratio of 2nd to 4th digit length: a predictor of sperm numbers and concentrations of testosterone, luteinizing hormone and oestrogen. Hum Reprod 13:3000-3004 6. Malas MA, Dogan S, Evcil EH, Desdicioglu K (2006) Fetal development of the hand, digits and digit ratio (2D:4D). Early Hum Dev 82:469-475 7. McIntyre MH, Ellison PT, Lieberman DE, Demerath E, Towne B (2005) The development of sex differences in digital formula from infancy in the Fels Longitudinal Study. Proc Biol Sci 272:1473-1479 8. Voracek M, Loibl LM (2009) Scientometric analysis and bibliography of digit ratio (2D:4D) research, 1998-2008. Psychol Rep 104:922-956 9. Manning JT, Baron-Cohen S, Wheelwright S, Sanders G (2001) The 2nd to 4th digit ratio and autism. Dev Med Child Neurol, 43:160-4 10. Stevenson JC, Everson PM, Williams DC, Hipskind G, Grimes M, Mahoney ER. (2007) Attention deficit/hyperactivity disorder (ADHD) symptoms and digit ratios in a college sample. Am J Hum Biol 19:41-50 11. Bang AK, Carlsen E, Holm M, Petersen JH, Skakkebaek NE, Jørgensen N (2005) A study of finger lengths, semen quality and sex hormones in 360 young men from the general Danish population. Hum Reprod, 20:3109-13 12 Manning JT and Bundred PE. (2000) The ratio of 2nd–4th digit length: a new predictor of disease predisposition? Med Hypotheses 54:855–7 13. Collaer ML, Reimers S, Manning JT (2007) Visuospatial performance on an internet line judgment task and potential hormonal markers: sex, sexual orientation, and 2D:4D. Arch Sex Behav 36:177-192 14. Manning JT, Robinson SJ (2003) 2nd to 4th digit ratio and a universal mean for prenatal testosterone in homosexual men. Med Hypotheses 61:303-306 15. Rahman Q and Wilson GD (2003) Sexual orientation and the 2nd to 4th finger length ratio: evidence for organising effects of sex hormones or developmental instability? Psychoneuroendocrinology 28:288-303 16. Honekopp J, Manning JT, Muller C (2006) Digit ratio (2D:4D) and physical fitness in males and females: Evidence for effects of prenatal androgens on sexually selected traits. Horm Behav 49:545-549 17. Matchock RL (2008) Low digit ratio (2D:4D) is associated with delayed menarche. Am J Hum Biol 20:487-489 18. Gobrogge KL, Breedlove SM, Klump KL (2008) Genetic and environmental influences on 2D:4D finger length ratios: a study of monozygotic and dizygotic male and female twins. Arch Sex Behav 37:112-118 19. Medland SE, Loehlin JC (2008) Multivariate genetic analyses of the 2D:4D ratio: examining the effects of hand and measurement technique in data from 757 twin families. Twin Res Hum Genet 11:335-341 20. Paul SN, Kato BS, Cherkas LF, Andrew T, Spector TD (2006) Heritability of the second to fourth digit ratio (2D:4D): A twin study. Twin Research and Human Genetics 9:215-219 21. Voracek M, Dressler SG (2007) Digit ratio (2D:4D) in twins: Heritability estimates and evidence for a masculinized trait expression in women from opposite-sex pairs. Psychological Reports 100:115-126 22. Manning JT, Bundred PE, Newton DJ, Flanagan BF (2003) The 2nd to 4th digit ratio and variation in the androgen receptor gene. Evolution and Human Behavior 24:399-405 23. Golding J, Pembrey M, Jones R (2001) ALSPAC--the Avon Longitudinal Study of Parents and Children. I. Study methodology. Paediatr Perinat Epidemiol 15:74-87 24. Wright MJ, Martin N (2004) Brisbane Adolescent Twin Study: outline of study methods and research projects. Australian Journal of Psychology 56:65-78 25. Timpson NJ, Tobias JH, Richards JB, Soranzo N, Duncan EL, Sims AM, Whittaker P, Kumanduri V, Zhai G, Glaser B, et al (2009) Common variants in the region around Osterix are associated with bone mineral density and growth in childhood. Hum Mol Genet 18:1510-1517 26. Medland S, Nyholt D, Painter J, McEvoy B, McRae A, Zhu G, Gordon S, Wray N, Ferreira M, Wright M, et al (Submitted) Common variants in the Trichohyalin gene are associated with straight hair in Europeans. American Journal of Human Genetics. 27. Ong KK, Elks CE, Li S, Zhao JH, Luan J, Andersen LB, Bingham SA, Brage S, Smith GD, Ekelund U, et al (2009) Genetic variation in LIN28B is associated with the timing of puberty. Nat Genet 41:729-733 28. Abecasis GR, Cherny SS, Cookson WO, and Cardon LR (2002) Merlin--rapid analysis of dense genetic maps using sparse gene flow trees. Nat Genet 30:97-101 29. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, et al (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81:559-575 30. Perry JR, Stolk L, Franceschini N, Lunetta KL, Zhai G, McArdle PF, Smith AV, Aspelund T, Bandinelli S, Boerwinkle E, et al (2009) Meta-analysis of genome-wide association data identifies two loci influencing age at menarche. Nat Genet 41:648-650 31. Viswanathan SR, Daley GQ, Gregory RI (2008) Selective blockade of microRNA processing by Lin28. Science 320:97-100 32. Lettre G, Jackson AU, Gieger C, Schumacher FR, Berndt SI, Sanna S, Eyheramendy S, Voight BF, Butler JL, Guiducci C, et al (2008) Identification of ten loci associated with height highlights new biological pathways in human growth. Nat Genet 40:584-591 33. Sulem P, Gudbjartsson DF, Rafnar T, Holm H, Olafsdottir EJ, Olafsdottir GH, Jonsson T, Alexandersen P, Feenstra B, Boyd HA, et al (2009) Genome-wide association study identifies sequence variants on 6q21 associated with age at menarche. Nat Genet 41:734-738 34. He C, Kraft P, Chen C, Buring JE, Pare G, Hankinson SE, Chanock SJ, Ridker PM, Hunter DJ, Chasman DI (2009) Genome-wide association studies identify loci associated with age at menarche and age at natural menopause. Nat Genet 41:724-728 35. Viswanathan SR, Powers JT, Einhorn W, Hoshida Y, Ng TL, Toffanin S, O'Sullivan M, Lu J, Phillips LA, Lockhart VL, et al (2009) Lin28 promotes transformation and is associated with advanced human malignancies. Nat Genet 41:843-848 36. Guo Y, Chen Y, Ito H, Watanabe A, Ge X, Kodama T, Aburatani H (2006) Identification and characterization of lin-28 homolog B (LIN28B) in human hepatocellular carcinoma. Gene 384:51-61 37. Onland-Moret NC, Peeters PH, van Gils CH, Clavel-Chapelon F, Key T, Tjonneland A, Trichopoulou A, Kaaks R, Manjer J, Panico S, et al (2005) Age at menarche in relation to adult height: the EPIC study. Am J Epidemiol 162:623-632 38. Guo Y, Chen Y, Ito H, Watanabe A, Ge X, Kodama T, Auratani H (2006) Identification and characterization of lin-28 homolog B (LIN28B) in human hepatocellular carcinoma. Gene 384:51-61 39. Lutchmaya S, Baron-Cohen S, Raggatt P, Knickmeyer R, Manning JT (2004) 2nd to 4th digit ratios, fetal testosterone and estradiol. Early Human Development 77:23-82
URI:	http://wrap.warwick.ac.uk/id/eprint/3863

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