Androgenetic alopecia: Identification of four genetic risk loci and evidence for the contribution of WNT signaling to its etiology

Stefanie Heilmann; Amy K. Kiefer; Nadine Fricker; Dmitriy Drichel; Axel M. Hillmer; Christine Herold; Joyce Y. Tung; Nicholas Eriksson; Silke Redler; Regina C. Betz; Rui Li; Ari Kárason; Dale R. Nyholt; Kijoung Song; Sita H. Vermeulen; Stavroula Kanoni; George Dedoussis; Nicholas G. Martin; Lambertus A. Kiemeney; Vincent Mooser; Kari Stefansson; J. Brent Richards; Tim Becker; Felix F. Brockschmidt; David A. Hinds; Markus M. Nöthen

doi:10.1038/jid.2013.43

Androgenetic alopecia: Identification of four genetic risk loci and evidence for the contribution of WNT signaling to its etiology

Stefanie Heilmann, Amy K. Kiefer, Nadine Fricker, Dmitriy Drichel, Axel M. Hillmer, Christine Herold, Joyce Y. Tung, Nicholas Eriksson, Silke Redler, Regina C. Betz, Rui Li, Ari Kárason, Dale R. Nyholt, Kijoung Song, Sita H. Vermeulen, Stavroula Kanoni, George Dedoussis, Nicholas G. Martin, Lambertus A. Kiemeney, Vincent MooserKari Stefansson, J. Brent Richards, Tim Becker, Felix F. Brockschmidt, David A. Hinds, Markus M. Nöthen

Faculty of Medicine

University of Iceland

Research output: Contribution to journal › Article › peer-review

Abstract

The pathogenesis of androgenetic alopecia (AGA, male-pattern baldness) is driven by androgens, and genetic predisposition is the major prerequisite. Candidate gene and genome-wide association studies have reported that single-nucleotide polymorphisms (SNPs) at eight different genomic loci are associated with AGA development. However, a significant fraction of the overall heritable risk still awaits identification. Furthermore, the understanding of the pathophysiology of AGA is incomplete, and each newly associated locus may provide novel insights into contributing biological pathways. The aim of this study was to identify unknown AGA risk loci by replicating SNPs at the 12 genomic loci that showed suggestive association (5 × 10^-8 <P<10^-5) with AGA in a recent meta-analysis. We analyzed a replication set comprising 2,759 cases and 2,661 controls of European descent to confirm the association with AGA at these loci. Combined analysis of the replication and the meta-analysis data identified four genome-wide significant risk loci for AGA on chromosomes 2q35, 3q25.1, 5q33.3, and 12p12.1. The strongest association signal was obtained for rs7349332 (P=3.55 × 10 ^-15) on chr2q35, which is located intronically in WNT10A. Expression studies in human hair follicle tissue suggest that WNT10A has a functional role in AGA etiology. Thus, our study provides genetic evidence supporting an involvement of WNT signaling in AGA development.

Original language	English
Pages (from-to)	1489-1496
Number of pages	8
Journal	Journal of Investigative Dermatology
Volume	133
Issue number	6
DOIs	https://doi.org/10.1038/jid.2013.43
Publication status	Published - Jun 2013

Bibliographical note

Funding Information: The study was supported by the Life & Brain GmbH. We thank all participants for their voluntary participation in this research study. We thank Lucie Florin for her technical assistance in extracting DNA, and Christine Schmael for her revision of the manuscript. Moreover, we thank all additional members of the MAAN consortium: Hreinn Stefansson, Daniel Glass, Sarah E Medland, Maria Dimitriou, Dawn Waterworth, Frank Geller, Veronique Bataille, Sibylle Eigelshoven, Sandra Hanneken, Susanne Moebus, Martin den Heijer, Grant W Montgomery, Panos Deloukas, Andrew C Heath, Patrick Sulem, Massimo Mangino, Peter Vollenweider, and Tim D Spector. RCB is the recipient of a Heisenberg Professorship from the German Research Foundation (DFG). MMN is the recipient of a grant from the Alfried Krupp von Bohlen und Halbach-Stiftung.

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Heilmann, S., Kiefer, A. K., Fricker, N., Drichel, D., Hillmer, A. M., Herold, C., Tung, J. Y., Eriksson, N., Redler, S., Betz, R. C., Li, R., Kárason, A., Nyholt, D. R., Song, K., Vermeulen, S. H., Kanoni, S., Dedoussis, G., Martin, N. G., Kiemeney, L. A., ... Nöthen, M. M. (2013). Androgenetic alopecia: Identification of four genetic risk loci and evidence for the contribution of WNT signaling to its etiology. Journal of Investigative Dermatology, 133(6), 1489-1496. https://doi.org/10.1038/jid.2013.43

@article{b7c012a212494616b98daf152a497c40,

title = "Androgenetic alopecia: Identification of four genetic risk loci and evidence for the contribution of WNT signaling to its etiology",

abstract = "The pathogenesis of androgenetic alopecia (AGA, male-pattern baldness) is driven by androgens, and genetic predisposition is the major prerequisite. Candidate gene and genome-wide association studies have reported that single-nucleotide polymorphisms (SNPs) at eight different genomic loci are associated with AGA development. However, a significant fraction of the overall heritable risk still awaits identification. Furthermore, the understanding of the pathophysiology of AGA is incomplete, and each newly associated locus may provide novel insights into contributing biological pathways. The aim of this study was to identify unknown AGA risk loci by replicating SNPs at the 12 genomic loci that showed suggestive association (5 × 10-8 -5) with AGA in a recent meta-analysis. We analyzed a replication set comprising 2,759 cases and 2,661 controls of European descent to confirm the association with AGA at these loci. Combined analysis of the replication and the meta-analysis data identified four genome-wide significant risk loci for AGA on chromosomes 2q35, 3q25.1, 5q33.3, and 12p12.1. The strongest association signal was obtained for rs7349332 (P=3.55 × 10 -15) on chr2q35, which is located intronically in WNT10A. Expression studies in human hair follicle tissue suggest that WNT10A has a functional role in AGA etiology. Thus, our study provides genetic evidence supporting an involvement of WNT signaling in AGA development.",

author = "Stefanie Heilmann and Kiefer, \{Amy K.\} and Nadine Fricker and Dmitriy Drichel and Hillmer, \{Axel M.\} and Christine Herold and Tung, \{Joyce Y.\} and Nicholas Eriksson and Silke Redler and Betz, \{Regina C.\} and Rui Li and Ari K{\'a}rason and Nyholt, \{Dale R.\} and Kijoung Song and Vermeulen, \{Sita H.\} and Stavroula Kanoni and George Dedoussis and Martin, \{Nicholas G.\} and Kiemeney, \{Lambertus A.\} and Vincent Mooser and Kari Stefansson and Richards, \{J. Brent\} and Tim Becker and Brockschmidt, \{Felix F.\} and Hinds, \{David A.\} and N{\"o}then, \{Markus M.\}",

note = "Funding Information: The study was supported by the Life \& Brain GmbH. We thank all participants for their voluntary participation in this research study. We thank Lucie Florin for her technical assistance in extracting DNA, and Christine Schmael for her revision of the manuscript. Moreover, we thank all additional members of the MAAN consortium: Hreinn Stefansson, Daniel Glass, Sarah E Medland, Maria Dimitriou, Dawn Waterworth, Frank Geller, Veronique Bataille, Sibylle Eigelshoven, Sandra Hanneken, Susanne Moebus, Martin den Heijer, Grant W Montgomery, Panos Deloukas, Andrew C Heath, Patrick Sulem, Massimo Mangino, Peter Vollenweider, and Tim D Spector. RCB is the recipient of a Heisenberg Professorship from the German Research Foundation (DFG). MMN is the recipient of a grant from the Alfried Krupp von Bohlen und Halbach-Stiftung.",

year = "2013",

month = jun,

doi = "10.1038/jid.2013.43",

language = "English",

volume = "133",

pages = "1489--1496",

journal = "Journal of Investigative Dermatology",

issn = "0022-202X",

publisher = "Elsevier B.V.",

number = "6",

}

Heilmann, S, Kiefer, AK, Fricker, N, Drichel, D, Hillmer, AM, Herold, C, Tung, JY, Eriksson, N, Redler, S, Betz, RC, Li, R, Kárason, A, Nyholt, DR, Song, K, Vermeulen, SH, Kanoni, S, Dedoussis, G, Martin, NG, Kiemeney, LA, Mooser, V, Stefansson, K, Richards, JB, Becker, T, Brockschmidt, FF, Hinds, DA & Nöthen, MM 2013, 'Androgenetic alopecia: Identification of four genetic risk loci and evidence for the contribution of WNT signaling to its etiology', Journal of Investigative Dermatology, vol. 133, no. 6, pp. 1489-1496. https://doi.org/10.1038/jid.2013.43

TY - JOUR

T1 - Androgenetic alopecia

T2 - Identification of four genetic risk loci and evidence for the contribution of WNT signaling to its etiology

AU - Heilmann, Stefanie

AU - Kiefer, Amy K.

AU - Fricker, Nadine

AU - Drichel, Dmitriy

AU - Hillmer, Axel M.

AU - Herold, Christine

AU - Tung, Joyce Y.

AU - Eriksson, Nicholas

AU - Redler, Silke

AU - Betz, Regina C.

AU - Li, Rui

AU - Kárason, Ari

AU - Nyholt, Dale R.

AU - Song, Kijoung

AU - Vermeulen, Sita H.

AU - Kanoni, Stavroula

AU - Dedoussis, George

AU - Martin, Nicholas G.

AU - Kiemeney, Lambertus A.

AU - Mooser, Vincent

AU - Stefansson, Kari

AU - Richards, J. Brent

AU - Becker, Tim

AU - Brockschmidt, Felix F.

AU - Hinds, David A.

AU - Nöthen, Markus M.

N1 - Funding Information: The study was supported by the Life & Brain GmbH. We thank all participants for their voluntary participation in this research study. We thank Lucie Florin for her technical assistance in extracting DNA, and Christine Schmael for her revision of the manuscript. Moreover, we thank all additional members of the MAAN consortium: Hreinn Stefansson, Daniel Glass, Sarah E Medland, Maria Dimitriou, Dawn Waterworth, Frank Geller, Veronique Bataille, Sibylle Eigelshoven, Sandra Hanneken, Susanne Moebus, Martin den Heijer, Grant W Montgomery, Panos Deloukas, Andrew C Heath, Patrick Sulem, Massimo Mangino, Peter Vollenweider, and Tim D Spector. RCB is the recipient of a Heisenberg Professorship from the German Research Foundation (DFG). MMN is the recipient of a grant from the Alfried Krupp von Bohlen und Halbach-Stiftung.

PY - 2013/6

Y1 - 2013/6

N2 - The pathogenesis of androgenetic alopecia (AGA, male-pattern baldness) is driven by androgens, and genetic predisposition is the major prerequisite. Candidate gene and genome-wide association studies have reported that single-nucleotide polymorphisms (SNPs) at eight different genomic loci are associated with AGA development. However, a significant fraction of the overall heritable risk still awaits identification. Furthermore, the understanding of the pathophysiology of AGA is incomplete, and each newly associated locus may provide novel insights into contributing biological pathways. The aim of this study was to identify unknown AGA risk loci by replicating SNPs at the 12 genomic loci that showed suggestive association (5 × 10-8 -5) with AGA in a recent meta-analysis. We analyzed a replication set comprising 2,759 cases and 2,661 controls of European descent to confirm the association with AGA at these loci. Combined analysis of the replication and the meta-analysis data identified four genome-wide significant risk loci for AGA on chromosomes 2q35, 3q25.1, 5q33.3, and 12p12.1. The strongest association signal was obtained for rs7349332 (P=3.55 × 10 -15) on chr2q35, which is located intronically in WNT10A. Expression studies in human hair follicle tissue suggest that WNT10A has a functional role in AGA etiology. Thus, our study provides genetic evidence supporting an involvement of WNT signaling in AGA development.

AB - The pathogenesis of androgenetic alopecia (AGA, male-pattern baldness) is driven by androgens, and genetic predisposition is the major prerequisite. Candidate gene and genome-wide association studies have reported that single-nucleotide polymorphisms (SNPs) at eight different genomic loci are associated with AGA development. However, a significant fraction of the overall heritable risk still awaits identification. Furthermore, the understanding of the pathophysiology of AGA is incomplete, and each newly associated locus may provide novel insights into contributing biological pathways. The aim of this study was to identify unknown AGA risk loci by replicating SNPs at the 12 genomic loci that showed suggestive association (5 × 10-8 -5) with AGA in a recent meta-analysis. We analyzed a replication set comprising 2,759 cases and 2,661 controls of European descent to confirm the association with AGA at these loci. Combined analysis of the replication and the meta-analysis data identified four genome-wide significant risk loci for AGA on chromosomes 2q35, 3q25.1, 5q33.3, and 12p12.1. The strongest association signal was obtained for rs7349332 (P=3.55 × 10 -15) on chr2q35, which is located intronically in WNT10A. Expression studies in human hair follicle tissue suggest that WNT10A has a functional role in AGA etiology. Thus, our study provides genetic evidence supporting an involvement of WNT signaling in AGA development.

UR - https://www.scopus.com/pages/publications/84878527535

U2 - 10.1038/jid.2013.43

DO - 10.1038/jid.2013.43

M3 - Article

SN - 0022-202X

VL - 133

SP - 1489

EP - 1496

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

IS - 6

ER -

Androgenetic alopecia: Identification of four genetic risk loci and evidence for the contribution of WNT signaling to its etiology

Abstract

Bibliographical note

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