Limb development genes underlie variation in human fingerprint patterns.

Fingerprints are of long-standing practical and cultural interest, but little is known about the mechanisms that underlie their variation. Using genome-wide scans in Han Chinese cohorts, we identified 18 loci associated with fingerprint type across the digits, including a genetic basis for the long-recognized "pattern-block" correlations among the middle three digits. In particular, we identified a variant near EVI1 that alters regulatory activity and established a role for EVI1 in dermatoglyph patterning in mice. Dynamic EVI1 expression during human development supports its role in shaping the limbs and digits, rather than influencing skin patterning directly. Trans-ethnic meta-analysis identified 43 fingerprint-associated loci, with nearby genes being strongly enriched for general limb development pathways. We also found that fingerprint patterns were genetically correlated with hand proportions. Taken together, these findings support the key role of limb development genes in influencing the outcome of fingerprint patterning.

Biomarkers of fetal conditions: Finger ridge-counts, facial fluctuating asymmetry, and digit ratio (2D:4D)-are they correlated in women?

OBJECTIVES: Fetal environmental conditions are crucial for life-long health. Direct measurements of developmental conditions are limited in humans; thus, several biomarkers of those conditions have been proposed: that is, finger ridge-counts, level of facial fluctuating asymmetry (FA), and digit ratio (2D:4D). Since all of these biomarkers share a similar gestational time of formation, we hypothesize that their values are significantly correlated. MATERIALS AND METHODS: Data were collected at the Mogielica Human Ecology Study Site in southern Poland among 234 women. Finger ridge-counts, level of facial FA, and 2D:4D have been measured. The two-step analyses included Pearson's correlations of simple values of the biomarkers and correlations of composite variables calculated based on principal component analysis. RESULTS: We did not find any statistically significant correlations between finger ridge-counts, FA, and 2D:4D in women. Similarly, we did not observe any correlations between three composites created from the biomarkers. DISCUSSION: Our results indicate that there are no relationships between the biomarkers, suggested as proxies of the quality of prenatal conditions, in a single population. This is the first study analyzing three different markers simultaneously. The lack of correlations may indicate that the tested biomarkers reflect, in fact, different environmental conditions, occurring in separate "critical windows" of development, or that the biomarkers are not valid as proxies of developmental conditions.

Understanding COVID-19: Digit ratio (2D:4D) and sex differences in national case fatality rates.

BACKGROUND: The reported national case fatality rates (CFRs) for coronavirus disease 2019 (COVID-19) shows a sex bias with males > females. The relative lengths of the index (2D) and ring (4D) fingers (digit ratio; 2D:4D) is a sexually dimorphic (males < females) proxy of fetal sex steroids (low 2D:4D indicates high prenatal testosterone/low prenatal estrogen). AIM: To examine sex-specific relationships of 2D:4D per nation with national values of COVID-19 CFRs. STUDY DESIGN: COVID-19 CFRs and the percent of male deaths were related to mean national (self-reported) 2D:4D by sex and hand from a large online survey (the BBC Internet Study). SUBJECTS: 103,482 men and 83,366 women. OUTCOME MEASURES: Relationships of mean national 2D:4D with CFRs from 41 countries and with national male death rates from 16 countries. RESULTS: Male right and left hand 2D:4D showed positive relationships with CFR. These relationships remained significant after removing the influence of female 2D:4D. A positive association of male right and left 2D:4D was detected with the percentage of male deaths. CONCLUSIONS: At the national level, high mean 2D:4D (indicating low prenatal testosterone/high prenatal estrogen) is associated with high CFRs and percent male mortality. At the individual level, high 2D:4D may be a risk factor for severity of COVID-19 in males. We speculate that male 2D:4D is a negative correlate for expression of the SARS-CoV2 receptor (ACE2).

Age-related changes to motor synergies in multi-joint and multi-finger manipulative skills: a meta-analysis.

PURPOSE: The aim of the current meta-analysis was to examine the extent to which there are differences in upper extremity motor synergies across different age groups in manipulative tasks. METHODS: The studies that used the uncontrolled manifold method to examine the effect of age on motor synergies in multi-joint and multi-finger tasks were selected. Sixteen relevant studies from 1154 articles were selected for the meta-analysis-4 and 12 studies considered multi-joint kinematics and multi-finger kinetic tasks respectively. RESULTS: The results of the meta-analysis suggested reduced strength of synergies in multi-finger task in older adults, but this was not the case for synergies in multi-joint task. Part of this age-related difference in finger function is related to the increased variability in total force in grasping tasks. However, reductions in the strength of multi-finger synergies in hand functions following ageing appear to depend on the characteristics of the task. CONCLUSIONS: These findings indicate that the cooperation among fingers to stabilise the total required force to apply for grasping and other fine motor skills is less efficient in older adults that might affect the quality of manipulative tasks.

Second to fourth digit ratio (2D:4D) in women with carpal tunnel syndrome.

BACKGROUND: Carpal tunnel syndrome (CTS), a median nerve compressive neuropathy at the wrist, is the most common entrapment nerve disorder. Sex is an important risk factor of CTS as this condition is to five times more common in women than in men (sex-hormone dependent). There are no studies concerning 2D:4D (biomarker of prenatal sex steroids exposure) in patients with CTS. AIM: Here we consider the relationship between 2D:4D and CTS in women. STUDY DESIGN AND METHODS: The study involved 90 female participants (40 with a severe CTS (the mean age - 52.78 yrs., SD 11.44) and 50 control women (the mean age - 47.2 yrs., SD 8.23)). Anthropometric measurements were performed and the following indices were calculated: BMI, WHR and right and left 2D:4D. RESULTS: A stepwise logistic regression model showed that higher WHR and lower right 2D:4D increase the risk of CTS in women (AUC = 0.8865). CONCLUSIONS: These associations may suggest a role for prenatal and post-natal sex-hormones in CTS development, i.e. in the context of oestrogen receptor activation (number and/or sensitivity) and the pattern of fat distribution. Further studies examining the role of hormonal influence in this disorder may help to plan prophylaxis of CTS (e.g. early HRT).

The association between 2D:4D ratio and aggression in children and adolescents: Cross-cultural and gender differences.

BACKGROUND: Two recent meta-analyses have suggested the association between digit ratio (2D:4D) and aggression is weak. This conclusion has been criticised because the meta-analyses conflate forms of aggression that show strong sex differences with those that do not, and most studies have considered post-pubertal participants. AIMS: We test the influence of 2D:4D and ethnicity in the expression of aggression in children and adolescents in four ethnic groups of European and African origin. STUDY DESIGN: Buss and Perry aggression questionnaire. Direct measurement of the 2nd and 4th digits. SUBJECTS: 1296 children and adolescents from Tanzania and Russia from 4 ethnic groups - Datoga, Meru, Russians, Tatars. RESULTS: There were ethnic and gender differences in ratings on aggression with boys consistently reporting more physical aggression. In all four samples right 2D:4D was significantly lower in boys, compared to girls. With regard to our total sample of boys, the right 2D:4D was significantly and negatively associated with self-ratings on physical aggression, but no association was found for left 2D:4D. No associations between 2D:4D and physical aggression were found for girls. Hostility was negatively correlated with 2D:4D for boys, and anger was positively correlated with 2D:4D in girls. CONCLUSION: Sex differences were strongest for right 2D:4D (boysgirls). Right 2D:4D was negatively related to physical aggression in boys only, suggesting possible relationship to prenatal androgenization.

The association between digit ratio (2D:4D) and overweight or obesity among Chinese children and adolescents: A cross-sectional study.

BACKGROUND: The aim of this study was to analyze the relationship between 2D:4D and childhood overweight or obesity, which might indirectly show the role of prenatal hormone in childhood overweight or obesity. METHODS: Using stratified cluster sampling approach, a school-based cross-sectional investigation was undertaken among 687 children and adolescents aged 8-15 years. Each participant's index finger (2D) and ring finger (4D) length, height, weight, testosterone, and estradiol levels were measured, and their dietary behaviors, physical and sedentary activities were also surveyed. RESULTS: The prevalence of overweight or obesity among children and adolescents aged 8- and 12-15 years was 36.0% and 25.9%, respectively (P < 0.05). There were no associations between 2D:4D and overweight or obesity in both boys and girls (P > 0.05). However, 2D and multiplying index of digit ratio and length (MIDRL) associated directly with overweight or obesity among boys (OR (95%CI) were 1.45 (1.00, 2.14), 1.46 (1.01, 2.11), respectively), and was indirectly related to overweight or obesity by testosterone (OR were 1.30, 1.26, respectively). CONCLUSIONS: In boys, 2D and MIDRL were directly related to overweight or obesity, and indirectly associated with overweight or obesity by testosterone, which suggested that prenatal hormone exposure might associate with overweight or obesity among boys.

2D:4D ratios as an indicator of intrauterine androgen exposure in children who stutter.

AIM: We aimed to explore whether there is a relationship between stuttering and digit ratio (2D:4D), which is thought to be a marker of prenatal testosterone exposure. METHODS: We evaluated a total of 90 children who stutter (CWS; n = 40 mild-to-moderate and n = 50 severe stutters) and 40 healthy peers (CWNS) as controls. We used the Clinical Global Impression-Severity (CGIS) scale to measure the severity of stuttering. We measured the lengths of index finger (2D) and ring finger (4D) of both hands directly and divided to calculate 2D:4D ratio. The difference between the right and the left hand 2D:4D ratio (DR-L) was also calculated. RESULT: Significant difference was found in right 2D:4D and the mean DR-L between the CWS and CWNS groups. Right 2D:4D was significantly lower in stuttering boys than in control boys, and in stuttering girls than control girls. Also, DR-L was significantly lower in stuttering boys than control boys. In ANOVA, there were significant differences between the mild-to-moderate, severe stuttering and control groups in terms of right 2D:4D and DR-L. Right hand 2D:4D and DR-L decreased from controls to severe stutterers. CONCLUSION: Our results suggest that lower right 2D:4D and DR-L were related to the presence and severity of stuttering in children, i.e. CWS had lower 2D:4D and DR-L than CWNS. Further large-scale prospective studies are needed to clarify the reliability of 2D:4D ratio as an indicator of fetal sex hormone exposure level and its relation with the presence and severity of stuttering in children.

The second to fourth digit ratio in patients with congenital IGF-1 Deficiency.

The relationship between the length of the second and fourth ring finger (2D:4D ratio) is a sexually dimorphic trait, higher in females than in males. It is established during early prenatal development under the influence of sex hormones, as demonstrated in numerous studies both in humans and in mice. The current study involves patients with congenital GH/IGF-1 deficiency, a population not yet investigated. The 2D:4D ratio was measured from hand x-rays and compared with normal hand x-rays taken from the Greulich & Pyle Atlas. The analyses of our results revealed that patients with congenital GH/IGF-1 deficiency show an identical 2D:4D ratio for both sexes, but a higher (more feminine) ratio than the normal population. These findings may be explained by a higher estrogen effect resulting from the absence of a functional GH-IGF-1 axis prenatally.

Association of the 2D:4D digit ratio with body composition among the Polish children aged 6-13 years.

The 2D:4D digit ratio is formed as a result of genetic factors but also prenatal exposure to sex hormones. The higher index value the higher concentration of the prenatal oestrogen. It is commonly known that testosterone is a hormone connected with muscle mass growth and that oestrogen affects adipogenesis. The aim of this study was to find if the digit ratio can be an informative indicator of the fat mass and muscle mass and body proportions in prepubertal children. Material and methods The analysed cohort included 420 children (221 girls and 199 boys) aged 6-13 years. Pearson's and Spearman's tests were conducted to assess whether 2D:4D was significantly correlated with the body composition measurements. Multiple regression models and stepwise forward regression were applied to select the most important independent variables affecting fat mass (%) and muscle mass (%) as well as the BMI and the WHR. Results The study shows that the digit ratio is negatively correlated with muscle mass (MM%) among girls (p < 0.05).There was no similar relationship in the group of boys. The regression models showed a significant role in determining the body composition and body proportions played by maternal factors such as: maternal level of education and weight gain during pregnancy. Conclusions The 2D:4D digit ratio seems to be an informative indicator of the muscle mass development since girls' early childhood. Moreover, maternal environment is also important in forming the offspring's body composition and proportions.

Sexual dimorphism in the ontogeny of second (2D) and fourth (4D) digit lengths, and digit ratio (2D:4D).

OBJECTIVE: Sex differences are often reported in digit lengths and digit ratio (2D:4D). However, the ontogeny of these sex differences and their interrelationships are less well known. METHODS: We considered sex differences in the lengths of the 2nd (2D) and 4th (4D) digit and 2D:4D in children aged 2 to 18 years (Sample I, n = 680) and adults aged 18 to 30 years (Sample II, n = 89,246). Digit length was determined by direct experimenter-measurement (Sample I) and direct self-measurement (Sample II). The data were tested with two-factor ANOVA's (sex and year-group). RESULTS: In both samples, there were significant main effects of sex and year-group, and a significant interaction effect on digit length. Digit length was positively related to age in both samples. Boys had longer digits than girls but only after 13 years. Men had longer digits than women and the dimorphism increased from 18 to 30 years. There were significant sex differences in 2D:4D (males < females), but no significant effect of age and no interaction effect of age and sex on 2D:4D in children or adults. CONCLUSIONS: Between 2 and 30 years, the lengths and the sexual dimorphisms of 2D and 4D are dependent on age. In contrast, 2D:4D is not age-dependent. We discuss our findings in the context of the ontogeny of digits and in the light of recent claims on the presence of static allometry in 2D and 4D lengths.

Genome-wide association study identifies nine novel loci for 2D:4D finger ratio, a putative retrospective biomarker of testosterone exposure in utero.

The ratio of the length of the index finger to that of the ring finger (2D:4D) is sexually dimorphic and is commonly used as a non-invasive biomarker of prenatal androgen exposure. Most association studies of 2D:4D ratio with a diverse range of sex-specific traits have typically involved small sample sizes and have been difficult to replicate, raising questions around the utility and precise meaning of the measure. In the largest genome-wide association meta-analysis of 2D:4D ratio to date (N = 15 661, with replication N = 75 821), we identified 11 loci (9 novel) explaining 3.8% of the variance in mean 2D:4D ratio. We also found weak evidence for association (ß = 0.06; P = 0.02) between 2D:4D ratio and sensitivity to testosterone [length of the CAG microsatellite repeat in the androgen receptor (AR) gene] in females only. Furthermore, genetic variants associated with (adult) testosterone levels and/or sex hormone-binding globulin were not associated with 2D:4D ratio in our sample. Although we were unable to find strong evidence from our genetic study to support the hypothesis that 2D:4D ratio is a direct biomarker of prenatal exposure to androgens in healthy individuals, our findings do not explicitly exclude this possibility, and pathways involving testosterone may become apparent as the size of the discovery sample increases further. Our findings provide new insight into the underlying biology shaping 2D:4D variation in the general population.

Digit ratios among the modern population of the Canary Islands

Sexual differences in the index to ring finger length ratio (2D:4D ratio) have been observed since more than 150 years ago, and they are already present in the foetus. Homeobox genes, which also control the differentiation of testes and ovaries, are involved in finger conformation, which is subjected to the influence of testosterone and estrogen levels. In general, women show larger 2D:4D digit ratios, although differences between sexes are subjected to ethnic variations. This study was performed in order to analyse the absolute values of several digit ratios (2D:4D; 4D:3D; 2D:3D) among 164 young adults of Tenerife (101 women). Finger lengths were directly measured dorsally using a calliper with an accuracy level of 0.01 mm. Dorsal digit lengths were defined as the distance between the fingertip and the dorsal base of the proximal phalanx, in a position in which fingers and palms formed an angle of 90º. We found that 2D:4D of both hands (for instance, women=0.9631 ± 0.02647; men= 0.9535 ± 0.02507 for the left 2D:4D ratios), the left 2D:3D (0.9063 ± 0.02216 in women; 0.8980 ± 0.01931 among men) and the right 4D:3D ratios (0.9377 ± 0.03625 among women vs 0.9471 ± 0.02138 among men) were significantly different among men and women. The magnitude of the difference among sexes is similar to that reported for other populations, and they allow for the elaboration of a discriminant function with an accuracy of 60.4%, that reaches 86% if stature is also included. We applied this discriminant function to a test group composed of 36 randomly selected women and 24 men, obtaining an accuracy of 58.33% and 81.67%, respectively

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Associations Between the 2nd to 4th Digit Ratio and Autism Spectrum Disorder in Population-Based Samples of Boys and Girls: Findings from the Study to Explore Early Development.

The ratio of the index (2nd) finger to ring (4th) finger lengths (2D:4D) is a proxy for fetal testosterone and estradiol. Studies suggesting 2D:4D is inversely associated with autism spectrum disorder (ASD) in males were limited by lack of confounder and subgroup assessments. Studies of females are sparse. We examined associations between ASD and 2D:4D among children in the Study to Explore Early Development; we considered case subgroups and numerous potential demographic and maternal-perinatal health confounders. We observed a modest inverse association between ASD and right-hand 2D:4D in males; subgroup analyses indicated associations were limited to ASD cases with birth defects/genetic syndromes or dysmorphic features. We observed a positive association between ASD and left-hand 2D:4D in females, overall and within most case subgroups.

Unintended activity in homologous muscle during intended unilateral contractions increases with greater task difficulty.

PURPOSE: The present study aimed to examine (1) the effect of task difficulty on unintended muscle activation (UIMA) levels in contralateral homologous muscle, (2) the difference between young and old adults in degree of UIMA with respect to task difficulty, and (3) temporal correlations between intended and contralateral unintended muscle activity at low frequency during unilateral intended force-matching tasks. METHODS: Twelve young (21.8 ± 2.4 years) and twelve old (69.9 ± 5.3 years) adult men performed steady isometric abductions with the left index finger at 20-80% of maximal voluntary contraction force. Two task difficulties were set by adjusting the spacing between two bars centered about the target force used for visual feedback on a monitor. The amplitude of surface electromyogram (aEMG) for both hands was calculated and normalized with respect to the maximal value. To determine if oscillations between intended and unintended muscle activities were correlated, cross-correlation function (CCF) of rectified EMG for both hands at low frequency was calculated for samples deemed adequate. RESULTS: The unintended aEMG (right hand) had significant main effects in task difficulty, age, and target force (all P < 0.05) without any interactions. Distinct significant peaks in CCF (0.38 on average, P < 0.05) with small time lags were present between rectified EMGs of intended and unintended muscles in 14 of the 17 samples. CONCLUSIONS: The current results indicate that UIMA increases with greater task difficulty regardless of age, and temporal correlations exist between intended and contralateral unintended muscle activities at low frequency.

Is early postnatal growth velocity, a proxy of minipubertal androgen action, related to adult second-to-fourth digit (2D:4D) ratios in men? A test in Cebu, Philippines.

OBJECTIVES: The ratio of the length of the second to the fourth digit (2D:4D) of the hand is often used as an index of prenatal androgen exposure but it might also be affected by androgens during "minipuberty," a period of temporarily high testosterone (T) production in the first few months of life. To examine this, we tested the prediction that men with lower 2D:4D ratios had greater weight growth velocities during the first months of life-a metric recently shown to correlate with concurrent T levels. METHODS: We related early growth data to 2D:4D ratios of both hands measured in 756 men (25-26 years) from Cebu, The Philippines. RESULTS: Birth-to-fourth-month (B4M) weight gain velocity (a proxy of early postnatal androgen action) was not associated with adult 2D:4D ratios of either hand, when the latter was measured continuously. When comparing men with more male-typical digit ratios (<1.0) to those with more female-typical ratios (≥ 1.0), the group of men with more male-typical ratios had greater B4M weight velocity, but this was only the case for the left hand. CONCLUSIONS: We found modest evidence that adult digit ratios relate to an anthropometric correlate of androgen exposure during minipuberty. Definitive assessment of the role of postnatal T in shaping digit ratios will require direct measures of perinatal T related to longitudinally assessed digit ratios.

Digit ratio (2D:4D) and muscular strength in adolescent boys.

Using a cross-sectional design, this study quantified the relationship between the digit ratio (2D:4D) and muscular strength in 57 adolescent boys. 2D:4D was very likely a moderate negative correlate of handgrip strength, even after adjustment for age and body size. This result may reflect the organizational benefits of prenatal testosterone.

Asymmetry and empathy: Higher asymmetry is associated with lower levels of mentalizing.

People differ in their mentalizing abilities. Though past research suggests that individual differences in exposure to prenatal testosterone may be able to explain why some people excel at mentalizing, while others struggle, meta-analyses yield a null relationship between 2D:4D ratio (a proxy for prenatal testosterone) and mentalizing. Importantly, however, past research has not examined the asymmetrical differences between the digit ratios on the right and left hands. In the current work, we test whether the difference between the digit ratios of the left and right hands may function as a better predictor of mentalizing than digit ratio alone. In Study 1, we begin by validating an online, self-report measure of 2D:4D ratio, providing test-retest reliability, convergent, and concurrent validity for our measure. In Study 2, we demonstrate that a) 2D:4D is quadratically related to asymmetry, b) asymmetry is negatively associated with mentalizing, and c) the relationship between asymmetry and mentalizing cannot be explained by the relationship between asymmetry and short-term memory. Taken together, our results paint a more nuanced picture of the relationship between digit ratio and mentalizing ability.

Is maternal periconceptional smoking associated with 2D:4D digit ratio in their children?

The 2nd--4th finger ratio (2D:4D) has been proposed as a potential indicator of greater androgen exposure during fetal development. Maternal periconceptional smoking may alter the homeostasis of fetal androgens, which could in turn result in differential development of 2D:4Ds in utero. The aim of the present study was to assess the effect of maternal periconceptional smoking (i.e. 1 year before through the first trimester of pregnancy) on the 2D:4D of children within The Maternal-Infant Research on Environmental Chemicals (MIREC) study. Maternal smoking history was obtained through questionnaires during the first trimester of pregnancy in 2001 women from 10 cities across Canada. The periconceptional smoking prevalence was 12%. A follow-up study was conducted to measure growth and development up to 5 years of age in a subsample of some 800 MIREC children (MIREC-CD Plus), and digital pictures of the ventral surface of both hands were obtained in mothers and children (2-5 years). The 2D:4D was calculated as the ratio of the 2nd and 4th fingers of each hand. Boys had lower mean 2D:4Ds compared with girls in both hands. Age and maternal 2D:4D were strong determinants of the children's 2D:4D, however, the mean 2D:4D did not differ among children whose mothers had smoked during the periconceptional period compared with those who had not, irrespective of sex. In conclusion, we did not find an association between maternal periconceptional smoking and children's 2D:4D, although the smoking prevalence was low.

Digit ratio (2D:4D) and handgrip strength are correlated in women (but not in men) in Hui ethnicity.

INTRODUCTION: Digit ratio, especially second-to-fourth digit ratio (2D:4D) is used as a biomarker of prenatal testosterone exposure and was found associated with physical ability, such as handgrip strength (HGS). Recently, this association has been discussed in several ethnic groups. AIMS: To investigate correlations between 2D:4D and HGS in Chinese population of Ningxia Hui ethnicity. METHODS: Here we firstly present the evidence on digit ratio and HGS of 346 college students (119 males and 227 females) by collecting photographs and HGS of both hands at Yinchuan city, in the Ningxia province of China. RESULTS: Females have higher mean values of digit ratio than males; significant variances of 3D:5D (left and right: P<0.05), 2D:3D, 3D:4D (left and right: P<0.01) and 2D:4D, 2D:5D (left and right: P<0.001) were found between different sex. Males showed significantly greater HGS than females on both hands. 2D:4D of both hands were significantly negative correlated with HGS in females (but not in males). CONCLUSIONS: 2D:4D ratio is negatively correlated with HGS in a Chinese population (especially in females) of Ningxia Hui ethnicity.