A Variant in LIN28B Is Associated with 2D:4D Finger-Length Ratio, a Putative Retrospective Biomarker of Prenatal Testosterone Exposure

Genetic Epidemiology, Queensland Institute of Medical Research, Australia.
The American Journal of Human Genetics (Impact Factor: 10.93). 03/2010; 86(4):519-25. DOI: 10.1016/j.ajhg.2010.02.017
Source: PubMed


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 x 10(-8)) and was subsequently independently replicated in an additional 3659 children from the ALSPAC cohort (p = 1.53 x 10(-6)). 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.

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    • "the formation of 2D:4D (Lawrance-Owen et al., 2013; Medland et al., 2010). Other potential genetic influences on 2D:4D values are proposed in the literature, i.e., a relationship between 2D:4D and a single variant in the LIN28B gene in a large group of children among whom a genome-wide single nucleotide polymorphism test was performed (Medland et al., 2010). Another possible gene suggested to play a significant role in determining 2D:4D value is SMOC1, which is crucial in limb development (Lawrance-Owen et al., 2013). "
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    ABSTRACT: Objectives: Second–to–fourth digit ratio (2D:4D) is proposed as a proxy for prenatal balance of sex hormones and is related to hormone–dependent characteristics in adult life, and a possible predictor of disease later in life. Here, we studied the relationship between 2D:4D and ovarian steroid hormones (17β–estradiol and progesterone) among women of reproductive age. Methods: 186 healthy, premenopausal women, aged 24–37 collected daily saliva samples during the entire menstrual cycle. Data on reproductive and lifestyle characteristics were collected via questionnaires and anthropometric measurements were performed. Results: No statistically significant relationships were detected between adult women’s sex hormone concentrations (17β–estradiol and progesterone) during the menstrual cycle and 2D:4D, in either left or right hand, when controlling for size at birth, BMI and physical activity. Conclusions: This study shows, for the first time in a large sample of reproductive age women, that 2D:4D is not a predictor of adult women’s sex hormone concentration. The lack of relationship may be due to the fact that 2D:4D might be genetically determined and is not related to maternal nutritional environment during fetal development. These results support the hypothesis that, in contrast to the quality of nutritional fetal environment, fetal hormonal environment (reflected by 2D:4D) does not determine reproductive physiology in later life.
    Full-text · Article · Mar 2015 · American Journal of Human Biology
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    • "It is also hypothesized that 2D:4D is genetically determined due to the presence of variant rs314277 located within intron 2 of the LIN28B gene (Medland et al., 2010) and expression of Hoxa or Hoxd genes. These Hox genes are responsible for differentiation of both the digits and the urinogenital system simultaneously (Manning et al., 2003), although this hypothesis still requires confirmation (Medland et al., 2010). Digit ratio (as a possible marker of pre-natal sex hormone levels) has been reported to correlate with male birth size (Danborno et al., 2010; McIntyre et al., 2006; Ronalds et al., 2002), adult body size (Fink et al., 2003; Van Dongen, 2009) and family size (Manning et al., 2003). "
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    ABSTRACT: Objectives: The 2nd to 4th digit ratio (2D:4D) is thought to reflect exposure to androgens during foetal development. This study examined the relationship between low (more masculine) and high (more feminine) 2D:4D and body size at different stages of the life course, adult testosterone levels and number of children among males. Methods: Five hundred and fifty-eight men from rural Poland at the Mogielica Human Ecology Study Site participated in this study. Life history data and anthropometric measurements were collected. Salivary morning and evening testosterone levels among 110 men from the same population were measured. Results: Low 2D:4D was related to higher birth weight (p = 0.04), higher birth length (p = 0.01), higher body mass during childhood and adolescence (p = 0.01), higher BMI (borderline significance, p = 0.06), higher number of children among fathers (p = 0.04) and higher testosterone levels during adulthood (p = 0.04). Conclusions: This study shows, for the first time in a single population, that digit ratio is related to sub-adult body size at different stages of the life course, adult testosterone levels and number of children. The observed results suggest that digit ratio might be a valuable predictor of male body size and reproductive characteristics.
    Full-text · Article · Apr 2014 · Annals of Human Biology
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    • "A study by Gobrogge et al.[13] reported substantial additive genetic and non-shared environmental influences on digit ratios. Moreover, a recent study by Medland et al.[14] showed that a variant situated in the intron 2 of LIN28B gene (rs314277) was associated with 2D:4D. Variation in 2D:4D has been suggested to have evolutionary relevance because of its associations with fitness components. "
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    ABSTRACT: Background: Ratio of second and fourth digit (2D:4D) is known to be germane in analyzing utero concentrations of testosterone and estrogen in human and other vertebrates. 2D:4D had been linked to several traits like athletes’ abilities, reproductive success, risk of cancer and cardiovascular disease (CVD). Metabolic syndrome (MetS) is a clustering of several cardiovascular risk factors. Waist circumference (WC), neck circumference (NC), body mass index (BMI) and waist-to-height ratio (WHtR) are important in measuring MetS. This study investigated sexual dimorphism in 2D:4D and its relationship with MetS indices and CVD factors among adult residing in Ilorin, North central Nigeria. Materials and Methods: This is a cross-sectional, stratified multi-staged sampling study. Participants residing in different neighborhoods were visited at home where finger lengths and anthropometric traits were measured. Participants include 801 healthy adults aged 18-44 years (56% male) who had been living in the area for more than 3 years. Results: Males showed significantly lower 2D:4D than females (unpaired t-test; t [699] = 11.49, P = 0.001). A significant positive correlation was observed in MetS markers and 2D:4D. WHtR showed the highest correlation with 2D:4D in male (r = 0.461, P ≤ 0.001) and female (r = 0.408, P ≤ 0.001) when compared with BMI, NC and WC. All positive correlations recorded in this study were high in male and right hand. Conclusion: Our results showed that 2D:4D is sexual dimorphic and right hand 2D:4D as a predictor of MetS is better. We concluded that 2D:4D is a proxy for MetS and CVD risk factors in Ilorin.
    Full-text · Article · Mar 2014 · Journal of research in medical sciences
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