title: DNA-based eye colour prediction across Europe with the IrisPlex system.
abstract: The ability to predict Externally Visible Characteristics (EVCs) from DNA, also referred to as Forensic DNA Phenotyping (FDP), is an exciting new chapter in forensic genetics holding great promise for tracing unknown individuals who are unidentifiable via standard forensic short tandem repeat (STR) profiling. For the purpose of DNA-based eye colour prediction, we previously developed the IrisPlex system consisting of a multiplex genotyping assay and a prediction model based on genotype and phenotype data from 3804 Dutch Europeans. Recently, we performed a forensic developmental validation study of the highly sensitive IrisPlex assay, which currently represents the only validated tool available for DNA-based prediction of eye colour in forensic applications. In the present study, we validate the IrisPlex prediction model by extending our initially described model towards genotype and phenotype data from multiple European populations. We performed IrisPlex analysis on 3840 individuals from seven sites across Europe as part of the European Eye (EUREYE) study for which DNA and high-resolution eye images were available. The accuracy rate of correctly predicting an individual's eye colour as being blue or brown, above the empirically established probability threshold of 0.7, was on average 94% across all seven European populations, ranging from 91% to 98%, despite the large variation in eye colour frequencies between the populations. The overall prediction accuracies expressed by the area under the receiver characteristic operating curves (AUC) were 0.96 for blue and 0.96 for brown eyes, which is considerably higher than those established before. The IrisPlex prediction model parameters generated from this multi-population European dataset, and thus its prediction capabilities, were highly comparable to those previously established. Therefore, the increased information regarding eye colour phenotype and genotype distributions across Europe, and the system's ability to provide eye colour predictions across Europe accurately, both highlight additional evidence for the utility of the IrisPlex system in forensic casework.
authors.affiliation: Department of Forensic Molecular Biology, Erasmus MC University Medical Centre Rotterdam, Rotterdam, The Netherlands.
authors.forename: Susan
authors.initials: S
authors.lastname: Walsh
authors.forename: Andreas
authors.initials: A
authors.lastname: Wollstein
authors.forename: Fan
authors.initials: F
authors.lastname: Liu
authors.forename: Usha
authors.initials: U
authors.lastname: Chakravarthy
authors.forename: Mati
authors.initials: M
authors.lastname: Rahu
authors.forename: Johan H
authors.initials: JH
authors.lastname: Seland
authors.forename: Gisele
authors.initials: G
authors.lastname: Soubrane
authors.forename: Laura
authors.initials: L
authors.lastname: Tomazzoli
authors.forename: Fotis
authors.initials: F
authors.lastname: Topouzis
authors.forename: Johannes R
authors.initials: JR
authors.lastname: Vingerling
authors.forename: Jesus
authors.initials: J
authors.lastname: Vioque
authors.forename: Astrid E
authors.initials: AE
authors.lastname: Fletcher
authors.forename: Kaye N
authors.initials: KN
authors.lastname: Ballantyne
authors.forename: Manfred
authors.initials: M
authors.lastname: Kayser
mesh_terms: D000368:Aged; D000951:Antigens, Neoplasm / Q000235:genetics; D017920:Antiporters / Q000235:genetics; D004247:DNA / Q000235:genetics*; D005060:Europe; D005127:Eye Color / Q000235:genetics*; D005838:Genotype; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics; D016015:Logistic Models; D026901:Membrane Transport Proteins / Q000235:genetics; D014442:Monophenol Monooxygenase / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D044767:Ubiquitin-Protein Ligases; D000099218:Interferon Regulatory Factor-4
chemical_list: D000951:Antigens, Neoplasm; D017920:Antiporters; D004247:DNA; D020662:Guanine Nucleotide Exchange Factors; D050835:Interferon Regulatory Factors; D026901:Membrane Transport Proteins; D014442:Monophenol Monooxygenase; D044767:Ubiquitin-Protein Ligases; D000099218:Interferon Regulatory Factor-4; C489600:OCA2 protein, human; C470570:SLC24A4 protein, human; C510061:SLC45A2 protein, human; C118566:HERC2 protein, human