Six Novel Susceptibility Loci for Early-Onset Androgenetic Alopecia and Their Unexpected Association with Common Diseases
Year: 2012
Type: article
Study design: Observational Study
Abstract: Androgenetic alopecia (AGA) is a highly heritable condition and the most common form of hair loss in humans. Susceptibility loci have been described on the X chromosome and chromosome 20, but these loci explain a minority of its heritable variance. We conducted a large-scale meta-analysis of seven genome-wide association studies for early-onset AGA in 12,806 individuals of European ancestry. While replicating the two AGA loci on the X chromosome and chromosome 20, six novel susceptibility loci reached genome-wide significance (p = 2.62×10⁻⁹-1.01×10⁻¹²). Unexpectedly, we identified a risk allele at 17q21.31 that was recently associated with Parkinson's disease (PD) at a genome-wide significant level. We then tested the association between early-onset AGA and the risk of PD in a cross-sectional analysis of 568 PD cases and 7,664 controls. Early-onset AGA cases had significantly increased odds of subsequent PD (OR = 1.28, 95% confidence interval: 1.06-1.55, p = 8.9×10⁻³). Further, the AGA susceptibility alleles at the 17q21.31 locus are on the H1 haplotype, which is under negative selection in Europeans and has been linked to decreased fertility. Combining the risk alleles of six novel and two established susceptibility loci, we created a genotype risk score and tested its association with AGA in an additional sample. Individuals in the highest risk quartile of a genotype score had an approximately six-fold increased risk of early-onset AGA [odds ratio (OR) = 5.78, p = 1.4×10⁻⁸⁸]. Our results highlight unexpected associations between early-onset AGA, Parkinson's disease, and decreased fertility, providing important insights into the pathophysiology of these conditions.
Source: PLoS Genetics
Authors: Rui Li, Felix F. Brockschmidt, Amy K. Kiefer, Hreinn Stefansson, Dale R. Nyholt, Kijoung Song, Sita H. Vermeulen, Stavroula Kanoni, Daniel Glass, Sarah E. Medland, Maria Dimitriou, Dawn Waterworth, Joyce Y. Tung, Frank Geller, Stefanie Heilmann, Axel M. Hillmer, Veronique Bataille, Sibylle Eigelshoven, Sandra Hanneken, Susanne Moebus, Christine Herold, Martin den Heijer, Grant W. Montgomery, Panos Deloukas, Nicholas Eriksson, Andrew C. Heath, Tim Becker, Patrick Sulem, Massimo Mangino, Peter Vollenweider, Tim D. Spector, George Dedoussis, Nicholas G. Martin, Lambertus A. Kiemeney, Vincent Mooser, Kari Stefansson, David A. Hinds, Markus M. Nöthen, J. Brent Richards
Institutions: Jewish General Hospital, Lady Davis Institute for Medical Research, McGill University, University of Bonn, Life & Brain (Germany), 23andMe (United States), deCODE Genetics (Iceland), QIMR Berghofer Medical Research Institute, GlaxoSmithKline (United States), Radboud University Medical Center, Wellcome Sanger Institute, King's College London, Harokopio University of Athens, Statens Serum Institut, Genome Institute of Singapore, Heinrich Heine University Düsseldorf, University of Duisburg-Essen, German Center for Neurodegenerative Diseases, Washington University in St. Louis, Institut für Medizinische Biometrie, Informatik und Epidemiologie, Centre Hospitalier Universitaire Vaudois, Netherlands Comprehensive Cancer Organisation
Language: English
Topic: Hair Growth and Disorders
Subfield: Urology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,043
Funders: National Science Foundation, GlaxoSmithKline, University of Michigan, Wellcome Trust, Chronic Disease Research Foundation, National Institute for Health and Care Research, King's College London, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Jewish General Hospital, Chinese Society of Clinical Oncology, Heinz Nixdorf Stiftung, National Institutes of Health, College of Pharmacy, University of Michigan, Canadian Institutes of Health Research, Medical Research Council, Australian Research Council, National Health and Medical Research Council, National Institute on Alcohol Abuse and Alcoholism, National Institute of Mental Health
Awards: G1151563582, G1207839733, G1436884665, G1583026501, G16286648, Validation and Replication of Genes Associated with Common Human Disease Using Australian Twin Families, G1853612974, G1916810480, Maximising knowledge from dense SNP (single nucleotide polymorphisms) data using multi-locus analysis, Cardiovascular diseases and psychiatric disorders in the general population: a prospective follow-up study, G2624192138, GENE-ENVIRONMENT INTERPLAY IN ALCOHOLISM, G2952053418, G2957143966, Molecular Epidemiology of Alcoholism 3 - EDAC Families, G3199409182, G3548961933, G3619332945, Identification of genetic risk factors for asthma: genome-wide association and the role of epigenetics, G3862454230, Genome-wide combined linkage-association scan of multiply phenotyped twin sibships, Pigmentation genes and melanoma risk, G4337057405, Genetics and prediction of complex disease risk, Association Screen of Migraine Candidate Genes, Molecular Epidemiology of Alcoholism 1: Candidate Gene, G5113003846, G5176409192, G5508833615, G5599442719, Mapping Genes for typical migraine using twin families., Genetics of moliness, Develop & improve methodology in gene mapping, targetting localisation of genes underlying migraine & other disorders, Quantitative and Molecular Genetic Analysis of Cognition, Uncoupled Research Fellowship, Genetics of moliness, G6994344002, Molecular Epidemiology of Alcoholism 2- Big Sibships, G7193217417, G7660237446, VARIATION IN THE EFFECTS OF ALCOHOL ON LIVER FUNCTION, Genetic Epidemiology of Pathological Gambling, G7857206400, G7894417573, Locating genes for elementary and complex cognitive abilities using genetic linkage and association analysis, G8253295407, G8378694876, G8471761114, PERSISTENCE AND CHANGE IN DRINKING HABITS--TWIN STUDY, G856913103, Statistical Methods and Algorithms for Analysis of High-throughput Genetics and Genomics Platforms
OpenAlex ID: W2096669722