title: Evaluation of the predictive capacity of DNA variants associated with straight hair in Europeans.
abstract: DNA-based prediction of hair morphology, defined as straight, curly or wavy hair, could contribute to an improved description of an unknown offender and allow more accurate forensic reconstructions of physical appearance in the field of forensic DNA phenotyping. Differences in scalp hair morphology are significant at the worldwide scale and within Europe. The only genome-wide association study made to date revealed the Trichohyalin gene (TCHH) to be significantly associated with hair morphology in Europeans and reported weaker associations for WNT10A and FRAS1 genes. We conducted a study that centered on six SNPs located in these three genes with a sample of 528 individuals from Poland. The predictive capacity of the candidate DNA variants was evaluated using logistic regression; classification and regression trees; and neural networks, by applying a 10-fold cross validation procedure. Additionally, an independent test set of 142 males from six European populations was used to verify performance of the developed prediction models. Our study confirmed association of rs11803731 (TCHH), rs7349332 (WNT10A) and rs1268789 (FRAS1) SNPs with hair morphology. The combined genotype risk score for straight hair had an odds ratio of 2.7 and these predictors explained ∼ 8.2% of the total variance. The selected three SNPs were found to predict straight hair with a high sensitivity but low specificity when a 10-fold cross validation procedure was applied and the best results were obtained using the neural networks approach (AUC=0.688, sensitivity=91.2%, specificity=23.0%). Application of the neural networks model with 65% probability threshold on an additional test set gave high sensitivity (81.4%) and improved specificity (50.0%) with a total of 78.7% correct calls, but a high non-classification rate (66.9%). The combined TTGGGG SNP genotype for rs11803731, rs7349332, rs1268789 (European frequency=4.5%) of all six straight hair-associated alleles was identified as the best predictor, giving >80% probability of straight hair. Finally, association testing of 44 SNPs previously identified to be associated with male pattern baldness revealed a suggestive association with hair morphology for rs4679955 on 3q25.1. The study results reported provide the starting point for the development of a predictive test for hair morphology in Europeans. More studies are now needed to discover additional determinants of hair morphology to improve the predictive accuracy of this trait in forensic analysis.
authors.affiliation: Department of Genetics and Evolution, Jagiellonian University, Krakow, Poland. Electronic address: ewelina.pospiech@uj.edu.pl.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Pośpiech
authors.affiliation: Faculty of Mathematics and Computer Science, Nicolaus Copernicus University, Toruń, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Karłowska-Pik
authors.affiliation: Institute of Forensic Research, Section of Forensic Genetics, Krakow, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Marcińska
authors.affiliation: Faculty of Life Sciences, King's College, London, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Abidi
authors.affiliation: Section of Forensic Genetics, Department of Forensic Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Jeppe Dyrberg
authors.initials: JD
authors.lastname: Andersen
authors.affiliation: Department of Human Biological Traces, Netherlands Forensic Institute, The Hague, The Netherlands.
authors.forename: Margreet van den
authors.initials: MVD
authors.lastname: Berge
authors.affiliation: Forensic Genetics Unit, Institute of Forensic Sciences, Faculty of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain; Genomic Medicine Group, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Institute of Health Carlos III, Spain.
authors.forename: Ángel
authors.initials: Á
authors.lastname: Carracedo
authors.affiliation: Institute of Legal Medicine, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Mayra
authors.initials: M
authors.lastname: Eduardoff
authors.affiliation: Forensic Genetics Unit, Institute of Forensic Sciences, Faculty of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Freire-Aradas
authors.affiliation: Section of Forensic Genetics, Department of Forensic Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Morling
authors.affiliation: Department of Human Biological Traces, Netherlands Forensic Institute, The Hague, The Netherlands.
authors.forename: Titia
authors.initials: T
authors.lastname: Sijen
authors.affiliation: Department of Dermatology, Medical College of Jagiellonian University, Krakow, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Skowron
authors.affiliation: Forensic Genetics Unit, Institute of Forensic Sciences, Faculty of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Jens
authors.initials: J
authors.lastname: Söchtig
authors.affiliation: Faculty of Life Sciences, King's College, London, UK.
authors.forename: Denise
authors.initials: D
authors.lastname: Syndercombe-Court
authors.affiliation: Department of Human Biological Traces, Netherlands Forensic Institute, The Hague, The Netherlands.
authors.forename: Natalie
authors.initials: N
authors.lastname: Weiler
authors.affiliation: Institute of Legal Medicine, Medical Faculty, University of Cologne, Cologne, Germany.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Schneider
authors.affiliation: Faculty of Life Sciences, King's College, London, UK.
authors.forename: David
authors.initials: D
authors.lastname: Ballard
authors.affiliation: Section of Forensic Genetics, Department of Forensic Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Claus
authors.initials: C
authors.lastname: Børsting
authors.affiliation: Institute of Legal Medicine, Medical University of Innsbruck, Innsbruck, Austria; Forensic Science Program, The Pennsylvania State University, University Park, Pennsylvania, USA.
authors.forename: Walther
authors.initials: W
authors.lastname: Parson
authors.affiliation: Forensic Genetics Unit, Institute of Forensic Sciences, Faculty of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Chris
authors.initials: C
authors.lastname: Phillips
authors.affiliation: Department of Genetics and Evolution, Jagiellonian University, Krakow, Poland; Institute of Forensic Research, Section of Forensic Genetics, Krakow, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Branicki
mesh_terms: D000941:Antigens / Q000235:genetics; D004247:DNA / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study; D006197:Hair; D006239:Haplotypes; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics; D008297:Male; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics*
chemical_list: D000941:Antigens; D007381:Intermediate Filament Proteins; C479420:TCHH protein, human; D004247:DNA
keywords: FRAS1; Forensic DNA phenotyping (FDP); Hair morphology; Neural networks; TCHH; WNT10A