Overlapping association signals in the genetics of hair-related phenotypes in humans and their relevance to predictive DNA analysis.

Genetic prediction of different hair phenotypes can help reconstruct the physical appearance of an individual whose biological sample is analyzed in criminal and identification cases. Up to date, forensic prediction models for hair colour, hair shape, hair loss and hair greying have been developed, but studies investigating predictability of hair thickness and density traits are missing. First data suggesting overlapping associations in various hair features have emerged in recent years, suggesting partially common genetic basis and molecular mechanisms, and this knowledge can be used for predictive purposes. Here we aim to broaden our understanding of the genetics underlying head, facial and body hair thickness and density traits and examine the association for a set of literature SNPs. We characterize the overlap in SNP association for various hair phenotypes, the extent of genetic interactions and the potential for genetic prediction. The study involved 999 samples from Poland, genotyped for 240 SNPs with targeted next-generation sequencing. Logistic regression methods were applied for association and prediction analyses while entropy-based approach was used for interaction testing. As a result, we refined known associations for monobrow and hairiness (PAX3, 5q13.2, TBX) and identified two novel association signals in IGFBP5 and VDR. Both genes were among top significant loci, showed broad association with different hair-related traits and were implicated in multiple interaction effects. Overall, for 14.7% of SNPs previously associated with head hair loss and/or hair shape, a positive signal of association was revealed with at least one hair feature studied in the current research. Overlap in association with at least two hair-related traits was demonstrated for 24 distinct loci. We showed that the associated SNPs explain ∼5-30% of the variation observed in particular hair traits and allow moderate accuracy of prediction. The highest accuracy was achieved for hairiness level prediction in females (AUC = 0.69 for the "none", 0.69 for the "low" and 0.76 for the "excessive" hairiness category) and monobrow (AUC = 0.69 for the "none", 0.62 for the "slight" and 0.70 for the "significant" monobrow category) with 33% of the variation in hairiness level in females explained by 7 SNPs and age, and 20% of the variation in monobrow captured by 7 SNPs and sex. Our study presents clear evidence of pleiotropy and epistasis in the genetics of hair traits. The acquired knowledge may have practical application in forensics, as well as in the cosmetic industry and anthropological research.

Dermoscopic features in different dermatopathological stages of cutaneous melanomas.

INTRODUCTION: Due to the rising incidence of cutaneous melanoma there is a great need for the development of new diagnostic techniques as well as the improvement of those that are already well known, such as dermoscopy. Since early detection and a proper technique for excising the tumor are crucial for patients' survival, early staging of the tumor is very important. AIM: To investigate whether there is a significant difference between the presence of selected dermoscopic features compared to the location on the skin and pathology results: Breslow's depth, mitotic index and ulceration. MATERIAL AND METHODS: We examined videodermoscopic images of cutaneous melanomas in 81 patients and compared their features with the histological results such as Breslow's depth, mitotic index and ulceration. In the study, we divided and compared the tumors in groups: in situ and invasive, ≤ 1.0 mm and > 1.0 mm thick on the Breslow scale. RESULTS: In the study we observed statistically significantly higher prevalence of pseudopods (30.5%) and multicomponent pattern (69.5%) in invasive melanomas in comparison to in situ melanomas (9.1% and 36.4% respectively). White regression structures were more commonly described in invasive melanomas thicker than 1.0 mm on Breslow's scale. Atypical blood vessels and nodules were more specific to invasive melanomas with ulcerations and mitotic index ≥ 1. The atypical pigment network was more specific for thin invasive melanomas. CONCLUSIONS: Presence of pseudopods, a multicomponent pattern, white regression structures, atypical blood vessels and nodules on dermoscopy suggest invasive (high stage) melanoma.

DNA-based predictive models for the presence of freckles.

Freckles or ephelides are hyperpigmented spots observed on skin surface mainly in European and Asian populations. Easy recognition and external visibility make prediction of ephelides, the potentially useful target in the field of forensic DNA phenotyping. Prediction of freckles would be a step forward in sketching the physical appearance of unknown perpetrators or decomposed cadavers for the forensic DNA intelligence purposes. Freckles are especially common in people with pale skin and red hair and therefore it is expected that predisposition to freckles may partially share the genetic background with other pigmentation traits. The first proposed freckle prediction model was developed based on investigation that involved variation of MC1R and 8 SNPs from 7 genes in a Spanish cohort [19]. In this study we examined 113 DNA variants from 46 genes previously associated with human pigmentation traits and assessed their impact on freckles presence in a group of 960 individuals from Poland. Nineteen DNA variants revealed associations with the freckle phenotype and the study also revealed that females have ∼1.8 higher odds of freckles presence comparing to males (p-value = 9.5 × 10-5). Two alternative prediction models were developed using regression methods. A simplified binomial 12-variable model predicts the presence of ephelides with cross-validated AUC = 0.752. A multinomial 14-variable model predicts one of three categories - non-freckled, medium freckled and heavily freckled. The two extreme categories, non-freckled and heavily freckled were predicted with moderately high accuracy of cross-validated AUC = 0.754 and 0.792, respectively. Prediction accuracy of the intermediate category was lower, AUC = 0.657. The study presents novel DNA models for prediction of freckles that can be used in forensic investigations and emphasizes significance of pigmentation genes and sex in predictive DNA analysis of freckles.

Global skin colour prediction from DNA.

Human skin colour is highly heritable and externally visible with relevance in medical, forensic, and anthropological genetics. Although eye and hair colour can already be predicted with high accuracies from small sets of carefully selected DNA markers, knowledge about the genetic predictability of skin colour is limited. Here, we investigate the skin colour predictive value of 77 single-nucleotide polymorphisms (SNPs) from 37 genetic loci previously associated with human pigmentation using 2025 individuals from 31 global populations. We identified a minimal set of 36 highly informative skin colour predictive SNPs and developed a statistical prediction model capable of skin colour prediction on a global scale. Average cross-validated prediction accuracies expressed as area under the receiver-operating characteristic curve (AUC) ± standard deviation were 0.97 ± 0.02 for Light, 0.83 ± 0.11 for Dark, and 0.96 ± 0.03 for Dark-Black. When using a 5-category, this resulted in 0.74 ± 0.05 for Very Pale, 0.72 ± 0.03 for Pale, 0.73 ± 0.03 for Intermediate, 0.87±0.1 for Dark, and 0.97 ± 0.03 for Dark-Black. A comparative analysis in 194 independent samples from 17 populations demonstrated that our model outperformed a previously proposed 10-SNP-classifier approach with AUCs rising from 0.79 to 0.82 for White, comparable at the intermediate level of 0.63 and 0.62, respectively, and a large increase from 0.64 to 0.92 for Black. Overall, this study demonstrates that the chosen DNA markers and prediction model, particularly the 5-category level; allow skin colour predictions within and between continental regions for the first time, which will serve as a valuable resource for future applications in forensic and anthropologic genetics.