title: Meta-analysis identifies novel risk loci and yields systematic insights into the biology of male-pattern baldness.
abstract: Male-pattern baldness (MPB) is a common and highly heritable trait characterized by androgen-dependent, progressive hair loss from the scalp. Here, we carry out the largest GWAS meta-analysis of MPB to date, comprising 10,846 early-onset cases and 11,672 controls from eight independent cohorts. We identify 63 MPB-associated loci (P<5 × 10-8, METAL) of which 23 have not been reported previously. The 63 loci explain ∼39% of the phenotypic variance in MPB and highlight several plausible candidate genes (FGF5, IRF4, DKK2) and pathways (melatonin signalling, adipogenesis) that are likely to be implicated in the key-pathophysiological features of MPB and may represent promising targets for the development of novel therapeutic options. The data provide molecular evidence that rather than being an isolated trait, MPB shares a substantial biological basis with numerous other human phenotypes and may deserve evaluation as an early prognostic marker, for example, for prostate cancer, sudden cardiac arrest and neurodegenerative disorders.
authors.affiliation: Institute of Human Genetics, University of Bonn, 53127 Bonn, Germany.|Department of Genomics, Life &Brain Center, University of Bonn, 53127 Bonn, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Heilmann-Heimbach
authors.affiliation: German Center for Neurodegenerative Disorders, 53175 Bonn, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Herold
authors.affiliation: Institute of Human Genetics, University of Bonn, 53127 Bonn, Germany.|Department of Genomics, Life &Brain Center, University of Bonn, 53127 Bonn, Germany.
authors.forename: Lara M
authors.initials: LM
authors.lastname: Hochfeld
authors.affiliation: Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, Singapore 138672, Singapore.|TRON-Translational Oncology at the University Medical Center of Johannes Gutenberg University, TRON gGmbH, 55131 Mainz, Germany.
authors.forename: Axel M
authors.initials: AM
authors.lastname: Hillmer
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, GPO Box 2434, Brisbane, Queensland 4001, Australia.
authors.forename: Dale R
authors.initials: DR
authors.lastname: Nyholt
authors.affiliation: Institute of Genomic Mathematics, University of Bonn, 53127 Bonn, Germany.
authors.forename: Julian
authors.initials: J
authors.lastname: Hecker
authors.affiliation: Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, Singapore 138672, Singapore.
authors.forename: Asif
authors.initials: A
authors.lastname: Javed
authors.affiliation: Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, Singapore 138672, Singapore.
authors.forename: Elaine G Y
authors.initials: EG
authors.lastname: Chew
authors.affiliation: Institute of Medical Informatics, Biometry and Epidemiology, Medical Faculty, University of Duisburg-Essen, 45122 Essen, Germany.
authors.forename: Sonali
authors.initials: S
authors.lastname: Pechlivanis
authors.affiliation: Cologne Center for Genomics, University of Cologne, 50931 Cologne, Germany.
authors.forename: Dmitriy
authors.initials: D
authors.lastname: Drichel
authors.affiliation: Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, Singapore 138672, Singapore.
authors.forename: Xiu Ting
authors.initials: XT
authors.lastname: Heng
authors.affiliation: Computational and Systems Biology, Genome Institute of Singapore, Singapore 138672, Singapore.
authors.forename: Ricardo C-H
authors.initials: RC
authors.lastname: Del Rosario
authors.affiliation: Institute of Genomic Mathematics, University of Bonn, 53127 Bonn, Germany.|Department of Biostatistics, Harvard School T.H. Chan of Public Health, Boston, Massachusetts 02115, USA.
authors.forename: Heide L
authors.initials: HL
authors.lastname: Fier
authors.affiliation: Dermatology Research Centre, Institute of Inflammation and Repair, University of Manchester, Manchester M13 9PL, UK.
authors.forename: Ralf
authors.initials: R
authors.lastname: Paus
authors.affiliation: Department of Computational Biology, University of Lausanne, 1011 Lausanne, Switzerland.|Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland.
authors.forename: Rico
authors.identifier: 0000-0002-6713-2214
authors.initials: R
authors.lastname: Rueedi
authors.affiliation: Radboud Institute for Health Sciences, Department for Health Evidence, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands.
authors.forename: Tessel E
authors.initials: TE
authors.lastname: Galesloot
authors.affiliation: Institute of Medical Informatics, Biometry and Epidemiology, Medical Faculty, University of Duisburg-Essen, 45122 Essen, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Moebus
authors.affiliation: Institute of Human Genetics, University of Bonn, 53127 Bonn, Germany.|Department of Genomics, Life &Brain Center, University of Bonn, 53127 Bonn, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Anhalt
authors.affiliation: Computational and Systems Biology, Genome Institute of Singapore, Singapore 138672, Singapore.
authors.forename: Shyam
authors.initials: S
authors.lastname: Prabhakar
authors.affiliation: Centre for Clinical Epidemiology, Departments of Medicine, Genetics and Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, Quebec, H3T 1E2 Canada.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.
authors.forename: Stavroula
authors.initials: S
authors.lastname: Kanoni
authors.affiliation: School of Health Sciences and Education, Department of Nutrition and Dietetics, Harokopio University, Attica, 17671 Kallithea, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Papanikolaou
authors.affiliation: Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland.|Institute of Social and Preventive Medicine, University Hospital of Lausanne, 1010 Lausanne, Switzerland.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Kutalik
authors.affiliation: William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.|Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah 21589, Saudi Arabia.
authors.forename: Panos
authors.identifier: 0000-0001-9251-070X
authors.initials: P
authors.lastname: Deloukas
authors.affiliation: Centre for Cell Biology and Cutaneous Research Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Philpott
authors.affiliation: Department of Internal Medicine, Lausanne University Hospital (CHUV), 1011 Lausanne, Switzerland.
authors.forename: Gérard
authors.initials: G
authors.lastname: Waeber
authors.affiliation: Department of Twin Research &Genetic Epidemiology, King's College London, London SE1 7EH, UK.
authors.forename: Tim D
authors.initials: TD
authors.lastname: Spector
authors.affiliation: Department of Internal Medicine, Lausanne University Hospital (CHUV), 1011 Lausanne, Switzerland.
authors.forename: Peter
authors.initials: P
authors.lastname: Vollenweider
authors.affiliation: Radboud Institute for Health Sciences, Department for Health Evidence, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands.
authors.forename: Lambertus A L M
authors.initials: LA
authors.lastname: Kiemeney
authors.affiliation: School of Health Sciences and Education, Department of Nutrition and Dietetics, Harokopio University, Attica, 17671 Kallithea, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Dedoussis
authors.affiliation: Centre for Clinical Epidemiology, Departments of Medicine, Genetics and Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, Quebec, H3T 1E2 Canada.|Department of Twin Research &Genetic Epidemiology, King's College London, London SE1 7EH, UK.
authors.forename: J Brent
authors.initials: JB
authors.lastname: Richards
authors.affiliation: Cologne Center for Genomics, University of Cologne, 50931 Cologne, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Nothnagel
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia.
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Martin
authors.affiliation: Institute for Community Medicine, Ernst Moritz Arndt University Greifswald, 17475 Greifswald, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Becker
authors.affiliation: 23andMe Inc., Mountain View, California 94040, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Hinds
authors.affiliation: Institute of Human Genetics, University of Bonn, 53127 Bonn, Germany.|Department of Genomics, Life &Brain Center, University of Bonn, 53127 Bonn, Germany.
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics; D050156:Adipogenesis / Q000235:genetics; D000505:Alopecia / Q000235:genetics*; D016022:Case-Control Studies; D051521:Fibroblast Growth Factor 5 / Q000235:genetics; D056726:Genetic Association Studies; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D050835:Interferon Regulatory Factors / Q000235:genetics; D008297:Male; D008550:Melatonin; D008565:Membrane Proteins / Q000235:genetics; D010641:Phenotype; D015398:Signal Transduction / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics; D000099218:Interferon Regulatory Factor-4
chemical_list: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; D051521:Fibroblast Growth Factor 5; D036341:Intercellular Signaling Peptides and Proteins; D050835:Interferon Regulatory Factors; D008550:Melatonin; D008565:Membrane Proteins; D015534:Trans-Activators; D000099218:Interferon Regulatory Factor-4; C498622:DKK2 protein, human; C081976:EBF1 protein, human; C496449:FGF5 protein, human; C548468:SRD5A2 protein, human