La maladie de Parkinson au Canada (serveur d'exploration)

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Six Novel Susceptibility Loci for Early-Onset Androgenetic Alopecia and Their Unexpected Association with Common Diseases

Identifieur interne : 001128 ( Main/Exploration ); précédent : 001127; suivant : 001129

Six Novel Susceptibility Loci for Early-Onset Androgenetic Alopecia and Their Unexpected Association with Common Diseases

Auteurs : Rui Li [Canada] ; Felix F. Brockschmidt [Allemagne] ; Amy K. Kiefer [États-Unis] ; Hreinn Stefansson [Islande] ; Dale R. Nyholt [Australie] ; Kijoung Song [États-Unis] ; Sita H. Vermeulen [Pays-Bas] ; Stavroula Kanoni [Royaume-Uni] ; Daniel Glass [Royaume-Uni] ; Sarah E. Medland [Australie] ; Maria Dimitriou [Grèce] ; Dawn Waterworth [États-Unis] ; Joyce Y. Tung [États-Unis] ; Frank Geller [Danemark] ; Stefanie Heilmann [Allemagne] ; Axel M. Hillmer [Singapour] ; Veronique Bataille [Royaume-Uni] ; Sibylle Eigelshoven [Allemagne] ; Sandra Hanneken [Allemagne] ; Susanne Moebus [Allemagne] ; Christine Herold [Allemagne] ; Martin Den Heijer [Pays-Bas] ; Grant W. Montgomery [Australie] ; Panos Deloukas [Royaume-Uni] ; Nicholas Eriksson [États-Unis] ; Andrew C. Heath [États-Unis] ; Tim Becker [Allemagne] ; Patrick Sulem [Islande] ; Massimo Mangino [Royaume-Uni] ; Peter Vollenweider [Suisse] ; Tim D. Spector [Royaume-Uni] ; George Dedoussis [Grèce] ; Nicholas G. Martin [Australie] ; Lambertus A. Kiemeney [Pays-Bas] ; Vincent Mooser [États-Unis] ; Kari Stefansson [Islande] ; David A. Hinds [États-Unis] ; Markus M. Nöthen [Allemagne] ; J. Brent Richards [Canada, Royaume-Uni]

Source :

RBID : PMC:3364959

English descriptors

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.


Url:
DOI: 10.1371/journal.pgen.1002746
PubMed: 22693459
PubMed Central: 3364959


Affiliations:


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</nlm:aff>
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<title xml:lang="en" level="a" type="main">Six Novel Susceptibility Loci for Early-Onset Androgenetic Alopecia and Their Unexpected Association with Common Diseases</title>
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<name sortKey="Li, Rui" sort="Li, Rui" uniqKey="Li R" first="Rui" last="Li">Rui Li</name>
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</nlm:aff>
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</nlm:aff>
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<addr-line>Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Genomics, Life and Brain Center, University of Bonn, Bonn</wicri:regionArea>
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<region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
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<name sortKey="Kiefer, Amy K" sort="Kiefer, Amy K" uniqKey="Kiefer A" first="Amy K." last="Kiefer">Amy K. Kiefer</name>
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<addr-line>23andMe, Mountain View, California, United States of America</addr-line>
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<addr-line>deCODE genetics, Reykjavík, Iceland</addr-line>
</nlm:aff>
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<addr-line>Queensland Institute of Medical Research, Brisbane, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Queensland Institute of Medical Research, Brisbane</wicri:regionArea>
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<name sortKey="Song, Kijoung" sort="Song, Kijoung" uniqKey="Song K" first="Kijoung" last="Song">Kijoung Song</name>
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<nlm:aff id="aff7">
<addr-line>Genetics Division, GlaxoSmithKline, King of Prussia, Pennsylvania, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
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<nlm:aff id="aff8">
<addr-line>Department of Epidemiology, Biostatistics, and HTA, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands</addr-line>
</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Epidemiology, Biostatistics, and HTA, Radboud University Nijmegen Medical Centre, Nijmegen</wicri:regionArea>
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<settlement type="city">Nimègue</settlement>
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<addr-line>Department of Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands</addr-line>
</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Genetics, Radboud University Nijmegen Medical Centre, Nijmegen</wicri:regionArea>
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<settlement type="city">Nimègue</settlement>
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<addr-line>Genetics of Complex Traits in Humans, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom</addr-line>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Genetics of Complex Traits in Humans, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton</wicri:regionArea>
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<name sortKey="Glass, Daniel" sort="Glass, Daniel" uniqKey="Glass D" first="Daniel" last="Glass">Daniel Glass</name>
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<nlm:aff id="aff11">
<addr-line>Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom</addr-line>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Twin Research and Genetic Epidemiology, King's College London, London</wicri:regionArea>
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<settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
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</placeName>
</affiliation>
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<name sortKey="Medland, Sarah E" sort="Medland, Sarah E" uniqKey="Medland S" first="Sarah E." last="Medland">Sarah E. Medland</name>
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<nlm:aff id="aff6">
<addr-line>Queensland Institute of Medical Research, Brisbane, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Queensland Institute of Medical Research, Brisbane</wicri:regionArea>
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<nlm:aff id="aff12">
<addr-line>Department of Dietetics-Nutrition, Harokopio University, Athens, Greece</addr-line>
</nlm:aff>
<country xml:lang="fr">Grèce</country>
<wicri:regionArea>Department of Dietetics-Nutrition, Harokopio University, Athens</wicri:regionArea>
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<settlement type="city">Athènes</settlement>
<settlement type="town">Kallithéa</settlement>
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</nlm:aff>
<country xml:lang="fr">États-Unis</country>
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<name sortKey="Tung, Joyce Y" sort="Tung, Joyce Y" uniqKey="Tung J" first="Joyce Y." last="Tung">Joyce Y. Tung</name>
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<nlm:aff id="aff4">
<addr-line>23andMe, Mountain View, California, United States of America</addr-line>
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<wicri:regionArea>23andMe, Mountain View, California</wicri:regionArea>
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<addr-line>Department of Epidemiology Research, Statens Serum Institute, Copenhagen, Denmark</addr-line>
</nlm:aff>
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<name sortKey="Heilmann, Stefanie" sort="Heilmann, Stefanie" uniqKey="Heilmann S" first="Stefanie" last="Heilmann">Stefanie Heilmann</name>
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</nlm:aff>
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<nlm:aff id="aff3">
<addr-line>Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Genomics, Life and Brain Center, University of Bonn, Bonn</wicri:regionArea>
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<region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
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<name sortKey="Hillmer, Axel M" sort="Hillmer, Axel M" uniqKey="Hillmer A" first="Axel M." last="Hillmer">Axel M. Hillmer</name>
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<nlm:aff id="aff14">
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</nlm:aff>
<country xml:lang="fr">Singapour</country>
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</affiliation>
</author>
<author>
<name sortKey="Bataille, Veronique" sort="Bataille, Veronique" uniqKey="Bataille V" first="Veronique" last="Bataille">Veronique Bataille</name>
<affiliation wicri:level="3">
<nlm:aff id="aff11">
<addr-line>Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom</addr-line>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Twin Research and Genetic Epidemiology, King's College London, London</wicri:regionArea>
<placeName>
<settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Eigelshoven, Sibylle" sort="Eigelshoven, Sibylle" uniqKey="Eigelshoven S" first="Sibylle" last="Eigelshoven">Sibylle Eigelshoven</name>
<affiliation wicri:level="3">
<nlm:aff id="aff15">
<addr-line>Department of Dermatology, University of Düsseldorf, Düsseldorf, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Dermatology, University of Düsseldorf, Düsseldorf</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Düsseldorf</region>
<settlement type="city">Düsseldorf</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Hanneken, Sandra" sort="Hanneken, Sandra" uniqKey="Hanneken S" first="Sandra" last="Hanneken">Sandra Hanneken</name>
<affiliation wicri:level="3">
<nlm:aff id="aff15">
<addr-line>Department of Dermatology, University of Düsseldorf, Düsseldorf, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Dermatology, University of Düsseldorf, Düsseldorf</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Düsseldorf</region>
<settlement type="city">Düsseldorf</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Moebus, Susanne" sort="Moebus, Susanne" uniqKey="Moebus S" first="Susanne" last="Moebus">Susanne Moebus</name>
<affiliation wicri:level="1">
<nlm:aff id="aff16">
<addr-line>Institute for Medical Informatics, Biometry, and Epidemiology, University Clinic Essen, University Duisburg-Essen, Essen, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute for Medical Informatics, Biometry, and Epidemiology, University Clinic Essen, University Duisburg-Essen, Essen</wicri:regionArea>
<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Herold, Christine" sort="Herold, Christine" uniqKey="Herold C" first="Christine" last="Herold">Christine Herold</name>
<affiliation wicri:level="3">
<nlm:aff id="aff17">
<addr-line>German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>German Center for Neurodegenerative Diseases (DZNE), Bonn</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Bonn</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Den Heijer, Martin" sort="Den Heijer, Martin" uniqKey="Den Heijer M" first="Martin" last="Den Heijer">Martin Den Heijer</name>
<affiliation wicri:level="3">
<nlm:aff id="aff18">
<addr-line>Department of Endocrinology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands</addr-line>
</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Endocrinology, Radboud University Nijmegen Medical Centre, Nijmegen</wicri:regionArea>
<placeName>
<settlement type="city">Nimègue</settlement>
<region type="province" nuts="2">Gueldre</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Montgomery, Grant W" sort="Montgomery, Grant W" uniqKey="Montgomery G" first="Grant W." last="Montgomery">Grant W. Montgomery</name>
<affiliation wicri:level="1">
<nlm:aff id="aff6">
<addr-line>Queensland Institute of Medical Research, Brisbane, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Queensland Institute of Medical Research, Brisbane</wicri:regionArea>
<wicri:noRegion>Brisbane</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Deloukas, Panos" sort="Deloukas, Panos" uniqKey="Deloukas P" first="Panos" last="Deloukas">Panos Deloukas</name>
<affiliation wicri:level="1">
<nlm:aff id="aff10">
<addr-line>Genetics of Complex Traits in Humans, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom</addr-line>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Genetics of Complex Traits in Humans, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton</wicri:regionArea>
<wicri:noRegion>Hinxton</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Eriksson, Nicholas" sort="Eriksson, Nicholas" uniqKey="Eriksson N" first="Nicholas" last="Eriksson">Nicholas Eriksson</name>
<affiliation wicri:level="2">
<nlm:aff id="aff4">
<addr-line>23andMe, Mountain View, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>23andMe, Mountain View, California</wicri:regionArea>
<placeName>
<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Heath, Andrew C" sort="Heath, Andrew C" uniqKey="Heath A" first="Andrew C." last="Heath">Andrew C. Heath</name>
<affiliation wicri:level="2">
<nlm:aff id="aff19">
<addr-line>Washington University Medical School, St. Louis, Missouri, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Washington University Medical School, St. Louis, Missouri</wicri:regionArea>
<placeName>
<region type="state">Missouri (État)</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Becker, Tim" sort="Becker, Tim" uniqKey="Becker T" first="Tim" last="Becker">Tim Becker</name>
<affiliation wicri:level="3">
<nlm:aff id="aff17">
<addr-line>German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>German Center for Neurodegenerative Diseases (DZNE), Bonn</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Bonn</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3">
<nlm:aff id="aff20">
<addr-line>Institute for Medical Biometry, Informatics, and Epidemiology, University of Bonn, Bonn, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute for Medical Biometry, Informatics, and Epidemiology, University of Bonn, Bonn</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Bonn</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Sulem, Patrick" sort="Sulem, Patrick" uniqKey="Sulem P" first="Patrick" last="Sulem">Patrick Sulem</name>
<affiliation wicri:level="1">
<nlm:aff id="aff5">
<addr-line>deCODE genetics, Reykjavík, Iceland</addr-line>
</nlm:aff>
<country xml:lang="fr">Islande</country>
<wicri:regionArea>deCODE genetics, Reykjavík</wicri:regionArea>
<wicri:noRegion>Reykjavík</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Mangino, Massimo" sort="Mangino, Massimo" uniqKey="Mangino M" first="Massimo" last="Mangino">Massimo Mangino</name>
<affiliation wicri:level="3">
<nlm:aff id="aff11">
<addr-line>Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom</addr-line>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Twin Research and Genetic Epidemiology, King's College London, London</wicri:regionArea>
<placeName>
<settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Vollenweider, Peter" sort="Vollenweider, Peter" uniqKey="Vollenweider P" first="Peter" last="Vollenweider">Peter Vollenweider</name>
<affiliation wicri:level="3">
<nlm:aff id="aff21">
<addr-line>Department of Internal Medicine, CHUV University Hospital, Lausanne, Switzerland</addr-line>
</nlm:aff>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>Department of Internal Medicine, CHUV University Hospital, Lausanne</wicri:regionArea>
<placeName>
<settlement type="city">Lausanne</settlement>
<region nuts="3" type="region">Canton de Vaud</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Spector, Tim D" sort="Spector, Tim D" uniqKey="Spector T" first="Tim D." last="Spector">Tim D. Spector</name>
<affiliation wicri:level="3">
<nlm:aff id="aff11">
<addr-line>Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom</addr-line>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Twin Research and Genetic Epidemiology, King's College London, London</wicri:regionArea>
<placeName>
<settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Dedoussis, George" sort="Dedoussis, George" uniqKey="Dedoussis G" first="George" last="Dedoussis">George Dedoussis</name>
<affiliation wicri:level="4">
<nlm:aff id="aff12">
<addr-line>Department of Dietetics-Nutrition, Harokopio University, Athens, Greece</addr-line>
</nlm:aff>
<country xml:lang="fr">Grèce</country>
<wicri:regionArea>Department of Dietetics-Nutrition, Harokopio University, Athens</wicri:regionArea>
<orgName type="university">Université Harokopio</orgName>
<placeName>
<settlement type="city">Athènes</settlement>
<settlement type="town">Kallithéa</settlement>
<region nuts="2" type="region">Attique</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Martin, Nicholas G" sort="Martin, Nicholas G" uniqKey="Martin N" first="Nicholas G." last="Martin">Nicholas G. Martin</name>
<affiliation wicri:level="1">
<nlm:aff id="aff6">
<addr-line>Queensland Institute of Medical Research, Brisbane, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Queensland Institute of Medical Research, Brisbane</wicri:regionArea>
<wicri:noRegion>Brisbane</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Kiemeney, Lambertus A" sort="Kiemeney, Lambertus A" uniqKey="Kiemeney L" first="Lambertus A." last="Kiemeney">Lambertus A. Kiemeney</name>
<affiliation wicri:level="3">
<nlm:aff id="aff8">
<addr-line>Department of Epidemiology, Biostatistics, and HTA, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands</addr-line>
</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Epidemiology, Biostatistics, and HTA, Radboud University Nijmegen Medical Centre, Nijmegen</wicri:regionArea>
<placeName>
<settlement type="city">Nimègue</settlement>
<region type="province" nuts="2">Gueldre</region>
</placeName>
</affiliation>
<affiliation wicri:level="3">
<nlm:aff id="aff22">
<addr-line>Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands</addr-line>
</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen</wicri:regionArea>
<placeName>
<settlement type="city">Nimègue</settlement>
<region type="province" nuts="2">Gueldre</region>
</placeName>
</affiliation>
<affiliation wicri:level="3">
<nlm:aff id="aff23">
<addr-line>Comprehensive Cancer Centre of the Netherlands (IKNL), Nijmegen, The Netherlands</addr-line>
</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Comprehensive Cancer Centre of the Netherlands (IKNL), Nijmegen</wicri:regionArea>
<placeName>
<settlement type="city">Nimègue</settlement>
<region type="province" nuts="2">Gueldre</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Mooser, Vincent" sort="Mooser, Vincent" uniqKey="Mooser V" first="Vincent" last="Mooser">Vincent Mooser</name>
<affiliation wicri:level="2">
<nlm:aff id="aff7">
<addr-line>Genetics Division, GlaxoSmithKline, King of Prussia, Pennsylvania, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Genetics Division, GlaxoSmithKline, King of Prussia, Pennsylvania</wicri:regionArea>
<placeName>
<region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Stefansson, Kari" sort="Stefansson, Kari" uniqKey="Stefansson K" first="Kari" last="Stefansson">Kari Stefansson</name>
<affiliation wicri:level="1">
<nlm:aff id="aff5">
<addr-line>deCODE genetics, Reykjavík, Iceland</addr-line>
</nlm:aff>
<country xml:lang="fr">Islande</country>
<wicri:regionArea>deCODE genetics, Reykjavík</wicri:regionArea>
<wicri:noRegion>Reykjavík</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Hinds, David A" sort="Hinds, David A" uniqKey="Hinds D" first="David A." last="Hinds">David A. Hinds</name>
<affiliation wicri:level="2">
<nlm:aff id="aff4">
<addr-line>23andMe, Mountain View, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>23andMe, Mountain View, California</wicri:regionArea>
<placeName>
<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Nothen, Markus M" sort="Nothen, Markus M" uniqKey="Nothen M" first="Markus M." last="Nöthen">Markus M. Nöthen</name>
<affiliation wicri:level="3">
<nlm:aff id="aff2">
<addr-line>Institute of Human Genetics, University of Bonn, Bonn, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute of Human Genetics, University of Bonn, Bonn</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Bonn</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3">
<nlm:aff id="aff3">
<addr-line>Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Genomics, Life and Brain Center, University of Bonn, Bonn</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Bonn</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3">
<nlm:aff id="aff17">
<addr-line>German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>German Center for Neurodegenerative Diseases (DZNE), Bonn</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Bonn</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Richards, J Brent" sort="Richards, J Brent" uniqKey="Richards J" first="J. Brent" last="Richards">J. Brent Richards</name>
<affiliation wicri:level="4">
<nlm:aff id="aff1">
<addr-line>Departments of Medicine, Human Genetics, Epidemiology, and Biostatistics, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, Quebec, Canada</addr-line>
</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Departments of Medicine, Human Genetics, Epidemiology, and Biostatistics, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, Quebec</wicri:regionArea>
<orgName type="university">Université McGill</orgName>
<placeName>
<settlement type="city">Montréal</settlement>
<region type="state">Québec</region>
</placeName>
</affiliation>
<affiliation wicri:level="3">
<nlm:aff id="aff11">
<addr-line>Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom</addr-line>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Twin Research and Genetic Epidemiology, King's College London, London</wicri:regionArea>
<placeName>
<settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
</affiliation>
</author>
</analytic>
<series>
<title level="j">PLoS Genetics</title>
<idno type="ISSN">1553-7390</idno>
<idno type="eISSN">1553-7404</idno>
<imprint>
<date when="2012">2012</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass>
<keywords scheme="KwdEn" xml:lang="en">
<term>Adult</term>
<term>Aged</term>
<term>Alleles</term>
<term>Alopecia (genetics)</term>
<term>Fertility (genetics)</term>
<term>Genetic Predisposition to Disease</term>
<term>Genome-Wide Association Study</term>
<term>Genotype</term>
<term>Haplotypes</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Parkinson Disease (genetics)</term>
<term>Polymorphism, Single Nucleotide</term>
<term>Risk Factors</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en">
<term>Alopecia</term>
<term>Fertility</term>
<term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Adult</term>
<term>Aged</term>
<term>Alleles</term>
<term>Genetic Predisposition to Disease</term>
<term>Genome-Wide Association Study</term>
<term>Genotype</term>
<term>Haplotypes</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Polymorphism, Single Nucleotide</term>
<term>Risk Factors</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<p>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
<sup>−9</sup>
–1.01×10
<sup>−12</sup>
). 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
<sup>−3</sup>
). 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
<sup>−88</sup>
]. Our results highlight unexpected associations between early-onset AGA, Parkinson's disease, and decreased fertility, providing important insights into the pathophysiology of these conditions.</p>
</div>
</front>
<back>
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<name sortKey="Ding, J" uniqKey="Ding J">J Ding</name>
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<li>Hovedstaden</li>
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<li>Lausanne</li>
<li>Londres</li>
<li>Montréal</li>
<li>Nimègue</li>
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