Six novel susceptibility Loci for early-onset androgenetic alopecia and their unexpected association with common diseases.
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 g...
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Public Library of Science (PLoS)
2012-05-01
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| Series: | PLoS Genetics |
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| author | 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 |
| author_facet | 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 |
| author_sort | Rui Li |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-9681c1f1d7c841d4900a974fc86ce27d |
| institution | DOAJ |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2012-05-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS Genetics |
| spelling | doaj-art-9681c1f1d7c841d4900a974fc86ce27d2025-08-20T02:57:31ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042012-05-0185e100274610.1371/journal.pgen.1002746Six novel susceptibility Loci for early-onset androgenetic alopecia and their unexpected association with common diseases.Rui LiFelix F BrockschmidtAmy K KieferHreinn StefanssonDale R NyholtKijoung SongSita H VermeulenStavroula KanoniDaniel GlassSarah E MedlandMaria DimitriouDawn WaterworthJoyce Y TungFrank GellerStefanie HeilmannAxel M HillmerVeronique BatailleSibylle EigelshovenSandra HannekenSusanne MoebusChristine HeroldMartin den HeijerGrant W MontgomeryPanos DeloukasNicholas ErikssonAndrew C HeathTim BeckerPatrick SulemMassimo ManginoPeter VollenweiderTim D SpectorGeorge DedoussisNicholas G MartinLambertus A KiemeneyVincent MooserKari StefanssonDavid A HindsMarkus M NöthenJ Brent RichardsAndrogenetic 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.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1002746&type=printable |
| spellingShingle | 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 Six novel susceptibility Loci for early-onset androgenetic alopecia and their unexpected association with common diseases. PLoS Genetics |
| title | Six novel susceptibility Loci for early-onset androgenetic alopecia and their unexpected association with common diseases. |
| title_full | Six novel susceptibility Loci for early-onset androgenetic alopecia and their unexpected association with common diseases. |
| title_fullStr | Six novel susceptibility Loci for early-onset androgenetic alopecia and their unexpected association with common diseases. |
| title_full_unstemmed | Six novel susceptibility Loci for early-onset androgenetic alopecia and their unexpected association with common diseases. |
| title_short | Six novel susceptibility Loci for early-onset androgenetic alopecia and their unexpected association with common diseases. |
| title_sort | six novel susceptibility loci for early onset androgenetic alopecia and their unexpected association with common diseases |
| url | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1002746&type=printable |
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