title: Evaluation of DNA variants associated with androgenetic alopecia and their potential to predict male pattern baldness.
abstract: Androgenetic alopecia, known in men as male pattern baldness (MPB), is a very conspicuous condition that is particularly frequent among European men and thus contributes markedly to variation in physical appearance traits amongst Europeans. Recent studies have revealed multiple genes and polymorphisms to be associated with susceptibility to MPB. In this study, 50 candidate SNPs for androgenetic alopecia were analyzed in order to verify their potential to predict MPB. Significant associations were confirmed for 29 SNPs from chromosomes X, 1, 5, 7, 18 and 20. A simple 5-SNP prediction model and an extended 20-SNP model were developed based on a discovery panel of 305 males from various European populations fitting one of two distinct phenotype categories. The first category consisted of men below 50 years of age with significant baldness and the second; men aged 50 years or older lacking baldness. The simple model comprised the five best predictors: rs5919324 near AR, rs1998076 in the 20p11 region, rs929626 in EBF1, rs12565727 in TARDBP and rs756853 in HDAC9. The extended prediction model added 15 SNPs from five genomic regions that improved overall prevalence-adjusted predictive accuracy measured by area under the receiver characteristic operating curve (AUC). Both models were evaluated for predictive accuracy using a test set of 300 males reflecting the general European population. Applying a 65% probability threshold, high prediction sensitivity of 87.1% but low specificity of 42.4% was obtained in men aged <50 years. In men aged ≥50, prediction sensitivity was slightly lower at 67.7% while specificity reached 90%. Overall, the AUC=0.761 calculated for men at or above 50 years of age indicates these SNPs offer considerable potential for the application of genetic tests to predict MPB patterns, adding a highly informative predictive system to the emerging field of forensic analysis of externally visible characteristics.
authors.affiliation: Institute of Forensic Research, Section of Forensic Genetics, Krakow, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Marcińska
authors.affiliation: Department of Genetics and Evolution, Jagiellonian University, Krakow, Poland.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Pośpiech
authors.affiliation: Faculty of Life Sciences, King's College, London, United Kingdom.
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
authors.initials: M
authors.lastname: van den Berge
authors.affiliation: Forensic Genetics Unit, Institute of Forensic Medicine, 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, Madrid, 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: Department of Analytical Biochemistry, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Marczakiewicz-Lustig
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 Medicine, 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, United Kingdom.
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, United Kingdom.
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, United States of America.
authors.forename: Walther
authors.initials: W
authors.lastname: Parson
authors.affiliation: Forensic Genetics Unit, Institute of Forensic Medicine, Faculty of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Chris
authors.initials: C
authors.lastname: Phillips
authors.affiliation: Institute of Forensic Research, Section of Forensic Genetics, Krakow, Poland; Department of Genetics and Evolution, Jagiellonian University, Krakow, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Branicki
mesh_terms: D000367:Age Factors; D000368:Aged; D000505:Alopecia / Q000175:diagnosis* / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012680:Sensitivity and Specificity; D044465:White People / Q000235:genetics