 Six Novel Susceptibility Loci for Early-Onset Androgenetic Alopecia and Their Unexpected Association with Common DiseasesRui 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 and J Brent Richards PLOS Genetics, 2012, vol. 8, issue 5, 1-9 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. Author Summary: While most genome-wide association studies (GWAS) focus on the identification of susceptibility loci for a specific disease, this hypothesis-free approach also enables the identification of unexpected associations between different diseases by taking advantage of the previously published GWAS associations. Androgenetic Alopecia (AGA, also known as male pattern baldness) is the most common type of hair loss in humans. Parkinson's disease is reported to occur more commonly in men than in women; however, there are no studies investigating the link between AGA and Parkinson's disease. Here, we show that a specific genetic locus, chromosome 17q21.31, which is associated with Parkinson's disease, is also a susceptibility locus for early-onset AGA. We further investigate the association between early-onset AGA and Parkinson's disease, irrespective of genotype, directly in a large-scale web-based study. We find that men with early-onset AGA have 28% higher risk of developing Parkinson's disease. The early-onset AGA locus on chromosome 17q21.31 has also been linked to decreased fertility previously. Future studies of this locus may implicate novel biological pathways affecting these three conditions. Date: 2012 Downloads: (external link) Related works: Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text Persistent link: https://EconPapers.repec.org/RePEc:plo:pgen00:1002746 DOI: 10.1371/journal.pgen.1002746 Access Statistics for this article More articles in PLOS Genetics from Public Library of Science |
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