Journal
PLOS GENETICS
Volume 8, Issue 5, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pgen.1002746
Keywords
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Categories
Funding
- Australian National Health and Medical Research Council (NHMRC) [241944, 339462, 389927, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 552485, 552498]
- Australian Research Council (ARC) [A7960034, A79906588, A79801419, DP0770096, DP0212016, DP0343921]
- EU [QLG2-CT-2002-01254]
- U.S. National Institutes of Health (NIH) [AA07535, AA10248, AA13320, AA13321, AA13326, AA14041, MH66206]
- Netherlands Scientific Organization [NWO 480-05-003]
- NHMRC
- ARC
- Swiss National Science Foundation [33CSCO-122661]
- GlaxoSmithKline
- Faculty of Biology and Medicine of Lausanne, Switzerland
- deCODE Genetics
- Wellcome Trust
- NIHR Biomedical Research Centre
- Chronic Disease Research Foundation
- Canadian Institutes of Health Research
- Canadian Foundation for Innovation
- Fonds de la Recherche en Sante Quebec
- Lady Davis Institute
- Jewish General Hospital
- Ministere du Developpement economique, de l'Innovation et de l'Exportation
- DHI Global Medical Group, Athens, Greece [174]
- Heinz Nixdorf Foundation
- German Ministry of Education and Science
- German Research Council [SI 236/8-1, SI236/9-1, ER 155/6-1]
- 23andMe
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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(-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 = 8.9x10(-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(-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.
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