Evaluation of DNA Variants Associated with Androgenetic Alopecia and Their Potential to Predict Male Pattern Baldness

Magdalena Marcińska; Ewelina Pośpiech; Sarah Abidi; Jeppe Dyrberg Andersen; Margreet van den Berge; Ángel Carracedo; Mayra Eduardoff; Anna Marczakiewicz-Lustig; Niels Morling; Titia Sijen; Małgorzata Skowron; Jens Söchtig; Denise Syndercombe-Court; Natalie Weiler; EUROFORGEN-NoE Consortium; Peter M Schneider; David Ballard; Claus Børsting; Walther Parson; Chris Phillips; Wojciech Branicki

doi:10.1371/journal.pone.0127852

Evaluation of DNA Variants Associated with Androgenetic Alopecia and Their Potential to Predict Male Pattern Baldness

Magdalena Marcińska, Ewelina Pośpiech, Sarah Abidi, Jeppe Dyrberg Andersen, Margreet van den Berge, Ángel Carracedo, Mayra Eduardoff, Anna Marczakiewicz-Lustig, Niels Morling, Titia Sijen, Małgorzata Skowron, Jens Söchtig, Denise Syndercombe-Court, Natalie Weiler, EUROFORGEN-NoE Consortium, Peter M Schneider, David Ballard, Claus Børsting, Walther Parson, Chris PhillipsWojciech Branicki

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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.

Original language	English
Article number	e0127852
Journal	PloS one
Volume	10
Issue number	5
Pages (from-to)	1-18
Number of pages	18
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0127852
Publication status	Published - 22 May 2015

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Marcińska, M., Pośpiech, E., Abidi, S., Andersen, J. D., van den Berge, M., Carracedo, Á., Eduardoff, M., Marczakiewicz-Lustig, A., Morling, N., Sijen, T., Skowron, M., Söchtig, J., Syndercombe-Court, D., Weiler, N., EUROFORGEN-NoE Consortium, Schneider, P. M., Ballard, D., Børsting, C., Parson, W., ... Branicki, W. (2015). Evaluation of DNA Variants Associated with Androgenetic Alopecia and Their Potential to Predict Male Pattern Baldness. PloS one, 10(5), 1-18. Article e0127852. https://doi.org/10.1371/journal.pone.0127852

Marcińska, M, Pośpiech, E, Abidi, S, Andersen, JD, van den Berge, M, Carracedo, Á, Eduardoff, M, Marczakiewicz-Lustig, A, Morling, N, Sijen, T, Skowron, M, Söchtig, J, Syndercombe-Court, D, Weiler, N, EUROFORGEN-NoE Consortium, Schneider, PM, Ballard, D, Børsting, C, Parson, W, Phillips, C & Branicki, W 2015, 'Evaluation of DNA Variants Associated with Androgenetic Alopecia and Their Potential to Predict Male Pattern Baldness', PloS one, vol. 10, no. 5, e0127852, pp. 1-18. https://doi.org/10.1371/journal.pone.0127852

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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.",

author = "Magdalena Marci{\'n}ska and Ewelina Po{\'s}piech and Sarah Abidi and Andersen, {Jeppe Dyrberg} and {van den Berge}, Margreet and {\'A}ngel Carracedo and Mayra Eduardoff and Anna Marczakiewicz-Lustig and Niels Morling and Titia Sijen and Ma{\l}gorzata Skowron and Jens S{\"o}chtig and Denise Syndercombe-Court and Natalie Weiler and {EUROFORGEN-NoE Consortium} and Schneider, {Peter M} and David Ballard and Claus B{\o}rsting and Walther Parson and Chris Phillips and Wojciech Branicki",

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T1 - Evaluation of DNA Variants Associated with Androgenetic Alopecia and Their Potential to Predict Male Pattern Baldness

AU - Marcińska, Magdalena

AU - Pośpiech, Ewelina

AU - Abidi, Sarah

AU - Andersen, Jeppe Dyrberg

AU - van den Berge, Margreet

AU - Carracedo, Ángel

AU - Eduardoff, Mayra

AU - Marczakiewicz-Lustig, Anna

AU - Morling, Niels

AU - Sijen, Titia

AU - Skowron, Małgorzata

AU - Söchtig, Jens

AU - Syndercombe-Court, Denise

AU - Weiler, Natalie

AU - EUROFORGEN-NoE Consortium

AU - Schneider, Peter M

AU - Ballard, David

AU - Børsting, Claus

AU - Parson, Walther

AU - Phillips, Chris

AU - Branicki, Wojciech

PY - 2015/5/22

Y1 - 2015/5/22

N2 - 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.

AB - 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.

U2 - 10.1371/journal.pone.0127852

DO - 10.1371/journal.pone.0127852

M3 - Journal article

C2 - 26001114

SN - 1932-6203

VL - 10

SP - 1

EP - 18

JO - PloS one

JF - PloS one

IS - 5

M1 - e0127852

ER -

Evaluation of DNA Variants Associated with Androgenetic Alopecia and Their Potential to Predict Male Pattern Baldness

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