The effect of gender on eye colour variation in European populations and an evaluation of the IrisPlex prediction model

Abstract

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. In this study, we investigate the role of gender as a factor that contributes to eye colour variation and suggest that the gender effect on eye colour is population specific.A total of 230 Italian individuals were typed for the six IrisPlex SNPs (rs12913832, rs1800407, rs12896399, rs1393350, rs16891982 and rs12203592). A quantitative eye colour score (Pixel Index of the Eye: PIE-score) was calculated based on digital eye images using the custom made DIAT software. The results were compared with those of Danish and Swedish population samples.As expected, we found HERC2 rs12913832 as the main predictor of human eye colour independently of ancestry. Furthermore, we found gender to be significantly associated with quantitative eye colour measurements in the Italian population sample. We found that the association was statistically significant only among Italian individuals typed as heterozygote GA for HERC2 rs12913832. Interestingly, we did not observe the same association in the Danish and Swedish population. This indicated that the gender effect on eye colour is population specific. We estimated the effect of gender on quantitative eye colour in the Italian population sample to be 4.9%. Among gender and the IrisPlex SNPs, gender ranked as the second most important predictor of human eye colour variation in Italians after HERC2 rs12913832. We, furthermore, tested the five lower ranked IrisPlex predictors, and evaluated all possible 3 6 (729) genotype combinations of the IrisPlex assay and their corresponding predictive values using the IrisPlex prediction model [4]. The results suggested that maximum three (rs12913832, rs1800407, rs16891982) of the six IrisPlex SNPs are useful in practical forensic genetic casework.

Forensic DNA Phenotyping: Predicting human appearance from crime scene material for investigative purposes

“…In a subsequent study, Pietroni et al [37] found gender to be significantly associated with quantitative eye color measurements in an Italian population sample, but not in a Danish and a Swedish sample. Notably, a gender effect on quantitative eye color was observed before by Liu et al [33], but in this study it only explained 0.04% of hue and 0.09% of saturation in the Dutch population studied, while in the Italian population analysed by Pietrone et al [37], gender explained 4.9% of the PIR-score that is based on saturation. Pietrone et al [37] concluded that the gender effect on eye color may be a population specific phenomenon.…”

“…The authors reemphasized that in their samples females tended to present darker eye colors than predicted by IrisPlex in a significantly higher proportion than males [41]. In a subsequent study, Pietroni et al [37] found gender to be significantly associated with quantitative eye color measurements in an Italian population sample, but not in a Danish and a Swedish sample. Notably, a gender effect on quantitative eye color was observed before by Liu et al [33], but in this study it only explained 0.04% of hue and 0.09% of saturation in the Dutch population studied, while in the Italian population analysed by Pietrone et al [37], gender explained 4.9% of the PIR-score that is based on saturation.…”

“…[32] favour the increase of SNP predictors for eye color over the 6-SNPs used with IrisPlex, Pietroni et al [37] recently suggested the opposite strategy. Referring to the tradition of "conservative statistical weight calculation" in the field of forensic genetics, and given the by far strongest eye color prediction effect known for HERC2 rs12913832 relative to all other current known SNP predictors for eye color, the authors suggested to limit DNA-based eye color prediction solely to HERC2 rs12913832 [37]. Without any statistical help (see text box 1), such ad hoc approach concludes blue eyes when the homozygote GG(CC) genotype is observed, brown eyes when the homozygote TT(AA) genotype is found, while all heterozygote individuals remain inconclusive [37].…”

“…Referring to the tradition of "conservative statistical weight calculation" in the field of forensic genetics, and given the by far strongest eye color prediction effect known for HERC2 rs12913832 relative to all other current known SNP predictors for eye color, the authors suggested to limit DNA-based eye color prediction solely to HERC2 rs12913832 [37]. Without any statistical help (see text box 1), such ad hoc approach concludes blue eyes when the homozygote GG(CC) genotype is observed, brown eyes when the homozygote TT(AA) genotype is found, while all heterozygote individuals remain inconclusive [37]. Although this approach was already applied earlier in the bone DNA identification of Nicolaus Copernicus and his HERC2-predicted blue eye color [38], further discussion in the field will show, if this rather simplistic view on DNA-based eye color prediction will be followed more widely.…”

“…Liu et al [33] exemplified that a GWAS on continuous eye color obtained from high-resolution digital eye images in thousands of Europeans allows the identification of additional genes and predictive SNPs that remained elusive in previous gene search studies using categorical eye color phenotypes. Some other studies too have been conducted to investigate quantitative eye color [37,46].…”