Six novel susceptibility Loci for early-onset androgenetic alopecia and their unexpected association with common diseases

Li, Rui, Brockschmidt, Felix F., Kiefer, Amy K., Stefansson, Hreinn, Nyholt, Dale R., Song, Kijoung, Vermeulen, Sita H., Kanoni, Stavroula, Glass, Daniel, Medland, Sarah E., Dimitriou, Maria, Waterworth, Dawn, Tung, Joyce Y., Geller, Frank, Heilmann, Stefanie, Hillmer, Axel M., Bataille, Veronique, Eigelshoven, Sibylle, Hanneken, Sandra, Moebus, Susanne, Herold, Christine, den Heijer, Martin, Montgomery, Grant W., Deloukas, Panos, Eriksson, Nicholas, Heath, Andrew C., Becker, Tim, Sulem, Patrick, Mangino, Massimo, Vollenweider, Peter, Spector, Tim D., Dedoussis, George, Martin, Nicholas G., Kiemeney, Lambertus A., Mooser, Vincent, Stefansson, Kari, Hinds, David A., Nöthen, Markus M., & Richards, J. Brent (2012) Six novel susceptibility Loci for early-onset androgenetic alopecia and their unexpected association with common diseases. PLoS Genet, 8(5), e1002746.

View at publisher (open access)


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 = 2.62x10(-)(9)-1.01x10(-)(1)(2)). 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 = 8.9x10(-)(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 = 1.4x10(-)(8)(8)]. Our results highlight unexpected associations between early-onset AGA, Parkinson's disease, and decreased fertility, providing important insights into the pathophysiology of these conditions.

Impact and interest:

35 citations in Scopus
29 citations in Web of Science®
Search Google Scholar™

Citation counts are sourced monthly from Scopus and Web of Science® citation databases.

These databases contain citations from different subsets of available publications and different time periods and thus the citation count from each is usually different. Some works are not in either database and no count is displayed. Scopus includes citations from articles published in 1996 onwards, and Web of Science® generally from 1980 onwards.

Citations counts from the Google Scholar™ indexing service can be viewed at the linked Google Scholar™ search.

Full-text downloads:

21 since deposited on 13 Jan 2016
2 in the past twelve months

Full-text downloads displays the total number of times this work’s files (e.g., a PDF) have been downloaded from QUT ePrints as well as the number of downloads in the previous 365 days. The count includes downloads for all files if a work has more than one.

ID Code: 91844
Item Type: Journal Article
Refereed: Yes
Keywords: Adult, Aged, Alleles, Alopecia/*genetics, Fertility/genetics, Genetic Predisposition to Disease, *Genome-Wide Association Study, Genotype, Haplotypes, Humans, Male, Middle Aged, Parkinson Disease/*genetics, Polymorphism, Single Nucleotide, Risk Factors
DOI: 10.1371/journal.pgen.1002746
ISSN: 1553-7404
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2012 Li et al.
Copyright Statement: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Deposited On: 13 Jan 2016 04:29
Last Modified: 26 Jun 2017 19:01

Export: EndNote | Dublin Core | BibTeX

Repository Staff Only: item control page