Rare variants analysis of cutaneous malignant melanoma genes in Parkinson's disease
Identifieur interne : 001B11 ( Ncbi/Merge ); précédent : 001B10; suivant : 001B12Rare variants analysis of cutaneous malignant melanoma genes in Parkinson's disease
Auteurs : S. J. Lubbe [Royaume-Uni] ; V. Escott-Price [Royaume-Uni] ; A. Brice [France] ; T. Gasser [Allemagne] ; A. M. Pittman [Royaume-Uni] ; J. Bras [Royaume-Uni] ; J. Hardy [Royaume-Uni] ; P. Heutink [Pays-Bas] ; N. M. Wood [Royaume-Uni] ; A. B. Singleton [États-Unis] ; D. G. Grosset [Royaume-Uni] ; C. B. Carroll [Royaume-Uni] ; M. H. Law [Australie] ; F. Demenais [France] ; M. M. Iles [Royaume-Uni] ; D. T. Bishop [Royaume-Uni] ; J. Newton-Bishop [Royaume-Uni] ; N. M. Williams [Royaume-Uni] ; H. R. Morris [Royaume-Uni]Source :
- Neurobiology of Aging [ 0197-4580 ] ; 2016.
Abstract
A shared genetic susceptibility between cutaneous malignant melanoma (CMM) and Parkinson's disease (PD) has been suggested. We investigated this by assessing the contribution of rare variants in genes involved in CMM to PD risk. We studied rare variation across 29 CMM risk genes using high-quality genotype data in 6875 PD cases and 6065 controls and sought to replicate findings using whole-exome sequencing data from a second independent cohort totaling 1255 PD cases and 473 controls. No statistically significant enrichment of rare variants across all genes, per gene, or for any individual variant was detected in either cohort. There were nonsignificant trends toward different carrier frequencies between PD cases and controls, under different inheritance models, in the following CMM risk genes:
Url:
DOI: 10.1016/j.neurobiolaging.2016.07.013
PubMed: 27640074
PubMed Central: 5096891
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<author><name sortKey="Singleton, A B" sort="Singleton, A B" uniqKey="Singleton A" first="A. B." last="Singleton">A. B. Singleton</name>
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<affiliation wicri:level="1"><nlm:aff id="aff10">Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth</wicri:regionArea>
<wicri:noRegion>Plymouth</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Law, M H" sort="Law, M H" uniqKey="Law M" first="M. H." last="Law">M. H. Law</name>
<affiliation wicri:level="1"><nlm:aff id="aff11">Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland</wicri:regionArea>
<wicri:noRegion>Queensland</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Demenais, F" sort="Demenais, F" uniqKey="Demenais F" first="F." last="Demenais">F. Demenais</name>
<affiliation wicri:level="3"><nlm:aff id="aff12">INSERM, UMR 946, Genetic Variation and Human Diseases Unit, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM, UMR 946, Genetic Variation and Human Diseases Unit, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="aff13">Institut Universitaire d'Hématologie, Université Paris Diderot, Sorbonne, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Institut Universitaire d'Hématologie, Université Paris Diderot, Sorbonne, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
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<author><name sortKey="Iles, M M" sort="Iles, M M" uniqKey="Iles M" first="M. M." last="Iles">M. M. Iles</name>
<affiliation wicri:level="1"><nlm:aff id="aff14">Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, Leeds, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, Leeds</wicri:regionArea>
<wicri:noRegion>Leeds</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Bishop, D T" sort="Bishop, D T" uniqKey="Bishop D" first="D. T." last="Bishop">D. T. Bishop</name>
<affiliation wicri:level="1"><nlm:aff id="aff14">Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, Leeds, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, Leeds</wicri:regionArea>
<wicri:noRegion>Leeds</wicri:noRegion>
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<author><name sortKey="Newton Bishop, J" sort="Newton Bishop, J" uniqKey="Newton Bishop J" first="J." last="Newton-Bishop">J. Newton-Bishop</name>
<affiliation wicri:level="1"><nlm:aff id="aff14">Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, Leeds, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, Leeds</wicri:regionArea>
<wicri:noRegion>Leeds</wicri:noRegion>
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<author><name sortKey="Williams, N M" sort="Williams, N M" uniqKey="Williams N" first="N. M." last="Williams">N. M. Williams</name>
<affiliation wicri:level="1"><nlm:aff id="aff2">Institute of Psychological Medicine and Clinical Neurosciences, Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, Cardiff University School of Medicine, Cardiff, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Institute of Psychological Medicine and Clinical Neurosciences, Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, Cardiff University School of Medicine, Cardiff</wicri:regionArea>
<wicri:noRegion>Cardiff</wicri:noRegion>
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</author>
<author><name sortKey="Morris, H R" sort="Morris, H R" uniqKey="Morris H" first="H. R." last="Morris">H. R. Morris</name>
<affiliation wicri:level="3"><nlm:aff id="aff1">Department of Clinical Neuroscience, UCL Institute of Neurology, London, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Clinical Neuroscience, UCL Institute of Neurology, London</wicri:regionArea>
<placeName><settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
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</analytic>
<series><title level="j">Neurobiology of Aging</title>
<idno type="ISSN">0197-4580</idno>
<idno type="eISSN">1558-1497</idno>
<imprint><date when="2016">2016</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>A shared genetic susceptibility between cutaneous malignant melanoma (CMM) and Parkinson's disease (PD) has been suggested. We investigated this by assessing the contribution of rare variants in genes involved in CMM to PD risk. We studied rare variation across 29 CMM risk genes using high-quality genotype data in 6875 PD cases and 6065 controls and sought to replicate findings using whole-exome sequencing data from a second independent cohort totaling 1255 PD cases and 473 controls. No statistically significant enrichment of rare variants across all genes, per gene, or for any individual variant was detected in either cohort. There were nonsignificant trends toward different carrier frequencies between PD cases and controls, under different inheritance models, in the following CMM risk genes: <italic>BAP1</italic>
, <italic>DCC</italic>
, <italic>ERBB4, KIT</italic>
, <italic>MAPK2</italic>
, <italic>MITF</italic>
, <italic>PTEN</italic>
, and <italic>TP53</italic>
. The very rare <italic>TYR</italic>
p.V275F variant, which is a pathogenic allele for recessive albinism, was more common in PD cases than controls in 3 independent cohorts. Tyrosinase, encoded by <italic>TYR,</italic>
is the rate-limiting enzyme for the production of neuromelanin, and has a role in the production of dopamine. These results suggest a possible role for another gene in the dopamine-biosynthetic pathway in susceptibility to neurodegenerative Parkinsonism, but further studies in larger PD cohorts are needed to accurately determine the role of these genes/variants in disease pathogenesis.</p>
</div>
</front>
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<affiliation wicri:level="3"><nlm:aff id="aff5">Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom</nlm:aff>
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<wicri:regionArea>Department of Molecular Neuroscience, UCL Institute of Neurology, London</wicri:regionArea>
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<wicri:regionArea>INSERM, UMR 946, Genetic Variation and Human Diseases Unit, Paris</wicri:regionArea>
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<region type="old region">Île-de-France</region>
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<affiliation wicri:level="3"><nlm:aff id="aff13">Institut Universitaire d'Hématologie, Université Paris Diderot, Sorbonne, Paris, France</nlm:aff>
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<author><name sortKey="Williams, N M" sort="Williams, N M" uniqKey="Williams N" first="N. M." last="Williams">N. M. Williams</name>
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<author><name sortKey="Morris, H R" sort="Morris, H R" uniqKey="Morris H" first="H. R." last="Morris">H. R. Morris</name>
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<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5096891</idno>
<idno type="RBID">PMC:5096891</idno>
<idno type="doi">10.1016/j.neurobiolaging.2016.07.013</idno>
<date when="2016">2016</date>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Rare variants analysis of cutaneous malignant melanoma genes in Parkinson's disease</title>
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<affiliation wicri:level="3"><nlm:aff id="aff1">Department of Clinical Neuroscience, UCL Institute of Neurology, London, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Clinical Neuroscience, UCL Institute of Neurology, 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>
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<affiliation wicri:level="1"><nlm:aff id="aff2">Institute of Psychological Medicine and Clinical Neurosciences, Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, Cardiff University School of Medicine, Cardiff, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Institute of Psychological Medicine and Clinical Neurosciences, Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, Cardiff University School of Medicine, Cardiff</wicri:regionArea>
<wicri:noRegion>Cardiff</wicri:noRegion>
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</author>
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<country xml:lang="fr">France</country>
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<wicri:noRegion>ICM</wicri:noRegion>
<wicri:noRegion>ICM</wicri:noRegion>
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<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, and DZNE, German Center for Neurodegenerative Diseases, Tübingen</wicri:regionArea>
<placeName><region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Tübingen</region>
<settlement type="city">Tübingen</settlement>
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<affiliation wicri:level="3"><nlm:aff id="aff5">Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Molecular Neuroscience, UCL Institute of Neurology, 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>
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<affiliation wicri:level="3"><nlm:aff id="aff5">Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Molecular Neuroscience, UCL Institute of Neurology, 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>
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<affiliation wicri:level="3"><nlm:aff id="aff5">Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Molecular Neuroscience, UCL Institute of Neurology, 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>
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<affiliation wicri:level="3"><nlm:aff id="aff6">Department of Clinical Genetics, Section of Medical Genomics, VU University Medical Centre, Amsterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Clinical Genetics, Section of Medical Genomics, VU University Medical Centre, Amsterdam</wicri:regionArea>
<placeName><settlement type="city">Amsterdam</settlement>
<region nuts="2" type="province">Hollande-Septentrionale</region>
</placeName>
</affiliation>
</author>
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<affiliation wicri:level="3"><nlm:aff id="aff5">Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Molecular Neuroscience, UCL Institute of Neurology, London</wicri:regionArea>
<placeName><settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="aff7">UCL Genetics Institute, London, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>UCL Genetics Institute, 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>
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<affiliation wicri:level="2"><nlm:aff id="aff8">Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
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<affiliation wicri:level="1"><nlm:aff id="aff9">Department of Neurology, Institute of Neurological Sciences, Queen Elizabeth University Hospital, Glasgow, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Neurology, Institute of Neurological Sciences, Queen Elizabeth University Hospital, Glasgow</wicri:regionArea>
<wicri:noRegion>Glasgow</wicri:noRegion>
</affiliation>
</author>
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<affiliation wicri:level="1"><nlm:aff id="aff10">Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth</wicri:regionArea>
<wicri:noRegion>Plymouth</wicri:noRegion>
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</author>
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<affiliation wicri:level="1"><nlm:aff id="aff11">Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland</wicri:regionArea>
<wicri:noRegion>Queensland</wicri:noRegion>
</affiliation>
</author>
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<affiliation wicri:level="3"><nlm:aff id="aff12">INSERM, UMR 946, Genetic Variation and Human Diseases Unit, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM, UMR 946, Genetic Variation and Human Diseases Unit, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="aff13">Institut Universitaire d'Hématologie, Université Paris Diderot, Sorbonne, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Institut Universitaire d'Hématologie, Université Paris Diderot, Sorbonne, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
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<affiliation wicri:level="1"><nlm:aff id="aff14">Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, Leeds, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, Leeds</wicri:regionArea>
<wicri:noRegion>Leeds</wicri:noRegion>
</affiliation>
</author>
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<affiliation wicri:level="1"><nlm:aff id="aff14">Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, Leeds, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, Leeds</wicri:regionArea>
<wicri:noRegion>Leeds</wicri:noRegion>
</affiliation>
</author>
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<affiliation wicri:level="1"><nlm:aff id="aff14">Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, Leeds, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, Leeds</wicri:regionArea>
<wicri:noRegion>Leeds</wicri:noRegion>
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<affiliation wicri:level="1"><nlm:aff id="aff2">Institute of Psychological Medicine and Clinical Neurosciences, Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, Cardiff University School of Medicine, Cardiff, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Institute of Psychological Medicine and Clinical Neurosciences, Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, Cardiff University School of Medicine, Cardiff</wicri:regionArea>
<wicri:noRegion>Cardiff</wicri:noRegion>
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</author>
<author><name sortKey="Morris, H R" sort="Morris, H R" uniqKey="Morris H" first="H. R." last="Morris">H. R. Morris</name>
<affiliation wicri:level="3"><nlm:aff id="aff1">Department of Clinical Neuroscience, UCL Institute of Neurology, London, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Clinical Neuroscience, UCL Institute of Neurology, London</wicri:regionArea>
<placeName><settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
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</analytic>
<series><title level="j">Neurobiology of Aging</title>
<idno type="ISSN">0197-4580</idno>
<idno type="eISSN">1558-1497</idno>
<imprint><date when="2016">2016</date>
</imprint>
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<front><div type="abstract" xml:lang="en"><p>A shared genetic susceptibility between cutaneous malignant melanoma (CMM) and Parkinson's disease (PD) has been suggested. We investigated this by assessing the contribution of rare variants in genes involved in CMM to PD risk. We studied rare variation across 29 CMM risk genes using high-quality genotype data in 6875 PD cases and 6065 controls and sought to replicate findings using whole-exome sequencing data from a second independent cohort totaling 1255 PD cases and 473 controls. No statistically significant enrichment of rare variants across all genes, per gene, or for any individual variant was detected in either cohort. There were nonsignificant trends toward different carrier frequencies between PD cases and controls, under different inheritance models, in the following CMM risk genes: <italic>BAP1</italic>
, <italic>DCC</italic>
, <italic>ERBB4, KIT</italic>
, <italic>MAPK2</italic>
, <italic>MITF</italic>
, <italic>PTEN</italic>
, and <italic>TP53</italic>
. The very rare <italic>TYR</italic>
p.V275F variant, which is a pathogenic allele for recessive albinism, was more common in PD cases than controls in 3 independent cohorts. Tyrosinase, encoded by <italic>TYR,</italic>
is the rate-limiting enzyme for the production of neuromelanin, and has a role in the production of dopamine. These results suggest a possible role for another gene in the dopamine-biosynthetic pathway in susceptibility to neurodegenerative Parkinsonism, but further studies in larger PD cohorts are needed to accurately determine the role of these genes/variants in disease pathogenesis.</p>
</div>
</front>
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<pubmed><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Rare variants analysis of cutaneous malignant melanoma genes in Parkinson's disease.</title>
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<country xml:lang="fr">Allemagne</country>
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<country xml:lang="fr">Royaume-Uni</country>
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<author><name sortKey="Hardy, J" sort="Hardy, J" uniqKey="Hardy J" first="J" last="Hardy">J. Hardy</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Molecular Neuroscience, UCL Institute of Neurology, London</wicri:regionArea>
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<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
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<author><name sortKey="Heutink, P" sort="Heutink, P" uniqKey="Heutink P" first="P" last="Heutink">P. Heutink</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Clinical Genetics, Section of Medical Genomics, VU University Medical Centre, Amsterdam, The Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Clinical Genetics, Section of Medical Genomics, VU University Medical Centre, Amsterdam</wicri:regionArea>
<placeName><settlement type="city">Amsterdam</settlement>
<region nuts="2" type="province">Hollande-Septentrionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Wood, N M" sort="Wood, N M" uniqKey="Wood N" first="N M" last="Wood">N M Wood</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom; UCL Genetics Institute, London, United Kingdom.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom; UCL Genetics Institute, 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="Singleton, A B" sort="Singleton, A B" uniqKey="Singleton A" first="A B" last="Singleton">A B Singleton</name>
<affiliation wicri:level="2"><nlm:affiliation>Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Grosset, D G" sort="Grosset, D G" uniqKey="Grosset D" first="D G" last="Grosset">D G Grosset</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Neurology, Institute of Neurological Sciences, Queen Elizabeth University Hospital, Glasgow, United Kingdom.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Neurology, Institute of Neurological Sciences, Queen Elizabeth University Hospital, Glasgow</wicri:regionArea>
<wicri:noRegion>Glasgow</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Carroll, C B" sort="Carroll, C B" uniqKey="Carroll C" first="C B" last="Carroll">C B Carroll</name>
<affiliation wicri:level="1"><nlm:affiliation>Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth, United Kingdom.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth</wicri:regionArea>
<wicri:noRegion>Plymouth</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Law, M H" sort="Law, M H" uniqKey="Law M" first="M H" last="Law">M H Law</name>
<affiliation wicri:level="1"><nlm:affiliation>Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland</wicri:regionArea>
<wicri:noRegion>Queensland</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Demenais, F" sort="Demenais, F" uniqKey="Demenais F" first="F" last="Demenais">F. Demenais</name>
<affiliation wicri:level="3"><nlm:affiliation>INSERM, UMR 946, Genetic Variation and Human Diseases Unit, Paris, France; Institut Universitaire d'Hématologie, Université Paris Diderot, Sorbonne, Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM, UMR 946, Genetic Variation and Human Diseases Unit, Paris, France; Institut Universitaire d'Hématologie, Université Paris Diderot, Sorbonne, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Iles, M M" sort="Iles, M M" uniqKey="Iles M" first="M M" last="Iles">M M Iles</name>
<affiliation wicri:level="1"><nlm:affiliation>Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, Leeds, United Kingdom.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, Leeds</wicri:regionArea>
<wicri:noRegion>Leeds</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Bishop, D T" sort="Bishop, D T" uniqKey="Bishop D" first="D T" last="Bishop">D T Bishop</name>
<affiliation wicri:level="1"><nlm:affiliation>Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, Leeds, United Kingdom.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, Leeds</wicri:regionArea>
<wicri:noRegion>Leeds</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Newton Bishop, J" sort="Newton Bishop, J" uniqKey="Newton Bishop J" first="J" last="Newton-Bishop">J. Newton-Bishop</name>
<affiliation wicri:level="1"><nlm:affiliation>Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, Leeds, United Kingdom.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, Leeds</wicri:regionArea>
<wicri:noRegion>Leeds</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Williams, N M" sort="Williams, N M" uniqKey="Williams N" first="N M" last="Williams">N M Williams</name>
<affiliation wicri:level="1"><nlm:affiliation>Institute of Psychological Medicine and Clinical Neurosciences, Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, Cardiff University School of Medicine, Cardiff, United Kingdom.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Institute of Psychological Medicine and Clinical Neurosciences, Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, Cardiff University School of Medicine, Cardiff</wicri:regionArea>
<wicri:noRegion>Cardiff</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Morris, H R" sort="Morris, H R" uniqKey="Morris H" first="H R" last="Morris">H R Morris</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Clinical Neuroscience, UCL Institute of Neurology, London, United Kingdom. Electronic address: h.morris@ucl.ac.uk.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Clinical Neuroscience, UCL Institute of Neurology, 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>
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<date when="2016">2016</date>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Rare variants analysis of cutaneous malignant melanoma genes in Parkinson's disease.</title>
<author><name sortKey="Lubbe, S J" sort="Lubbe, S J" uniqKey="Lubbe S" first="S J" last="Lubbe">S J Lubbe</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Clinical Neuroscience, UCL Institute of Neurology, London, United Kingdom.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Clinical Neuroscience, UCL Institute of Neurology, 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="Escott Price, V" sort="Escott Price, V" uniqKey="Escott Price V" first="V" last="Escott-Price">V. Escott-Price</name>
<affiliation wicri:level="1"><nlm:affiliation>Institute of Psychological Medicine and Clinical Neurosciences, Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, Cardiff University School of Medicine, Cardiff, United Kingdom.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Institute of Psychological Medicine and Clinical Neurosciences, Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, Cardiff University School of Medicine, Cardiff</wicri:regionArea>
<wicri:noRegion>Cardiff</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Brice, A" sort="Brice, A" uniqKey="Brice A" first="A" last="Brice">A. Brice</name>
<affiliation wicri:level="1"><nlm:affiliation>INSERM U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle Epinière, ICM, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle Epinière, ICM</wicri:regionArea>
<wicri:noRegion>ICM</wicri:noRegion>
<wicri:noRegion>ICM</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Gasser, T" sort="Gasser, T" uniqKey="Gasser T" first="T" last="Gasser">T. Gasser</name>
<affiliation wicri:level="3"><nlm:affiliation>Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, and DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, and DZNE, German Center for Neurodegenerative Diseases, Tübingen</wicri:regionArea>
<placeName><region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Tübingen</region>
<settlement type="city">Tübingen</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Pittman, A M" sort="Pittman, A M" uniqKey="Pittman A" first="A M" last="Pittman">A M Pittman</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Molecular Neuroscience, UCL Institute of Neurology, 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="Bras, J" sort="Bras, J" uniqKey="Bras J" first="J" last="Bras">J. Bras</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Molecular Neuroscience, UCL Institute of Neurology, 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="Hardy, J" sort="Hardy, J" uniqKey="Hardy J" first="J" last="Hardy">J. Hardy</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Molecular Neuroscience, UCL Institute of Neurology, 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="Heutink, P" sort="Heutink, P" uniqKey="Heutink P" first="P" last="Heutink">P. Heutink</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Clinical Genetics, Section of Medical Genomics, VU University Medical Centre, Amsterdam, The Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Clinical Genetics, Section of Medical Genomics, VU University Medical Centre, Amsterdam</wicri:regionArea>
<placeName><settlement type="city">Amsterdam</settlement>
<region nuts="2" type="province">Hollande-Septentrionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Wood, N M" sort="Wood, N M" uniqKey="Wood N" first="N M" last="Wood">N M Wood</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom; UCL Genetics Institute, London, United Kingdom.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom; UCL Genetics Institute, 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="Singleton, A B" sort="Singleton, A B" uniqKey="Singleton A" first="A B" last="Singleton">A B Singleton</name>
<affiliation wicri:level="2"><nlm:affiliation>Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Grosset, D G" sort="Grosset, D G" uniqKey="Grosset D" first="D G" last="Grosset">D G Grosset</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Neurology, Institute of Neurological Sciences, Queen Elizabeth University Hospital, Glasgow, United Kingdom.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Neurology, Institute of Neurological Sciences, Queen Elizabeth University Hospital, Glasgow</wicri:regionArea>
<wicri:noRegion>Glasgow</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Carroll, C B" sort="Carroll, C B" uniqKey="Carroll C" first="C B" last="Carroll">C B Carroll</name>
<affiliation wicri:level="1"><nlm:affiliation>Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth, United Kingdom.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth</wicri:regionArea>
<wicri:noRegion>Plymouth</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Law, M H" sort="Law, M H" uniqKey="Law M" first="M H" last="Law">M H Law</name>
<affiliation wicri:level="1"><nlm:affiliation>Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland</wicri:regionArea>
<wicri:noRegion>Queensland</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Demenais, F" sort="Demenais, F" uniqKey="Demenais F" first="F" last="Demenais">F. Demenais</name>
<affiliation wicri:level="3"><nlm:affiliation>INSERM, UMR 946, Genetic Variation and Human Diseases Unit, Paris, France; Institut Universitaire d'Hématologie, Université Paris Diderot, Sorbonne, Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM, UMR 946, Genetic Variation and Human Diseases Unit, Paris, France; Institut Universitaire d'Hématologie, Université Paris Diderot, Sorbonne, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Iles, M M" sort="Iles, M M" uniqKey="Iles M" first="M M" last="Iles">M M Iles</name>
<affiliation wicri:level="1"><nlm:affiliation>Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, Leeds, United Kingdom.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, Leeds</wicri:regionArea>
<wicri:noRegion>Leeds</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Bishop, D T" sort="Bishop, D T" uniqKey="Bishop D" first="D T" last="Bishop">D T Bishop</name>
<affiliation wicri:level="1"><nlm:affiliation>Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, Leeds, United Kingdom.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, Leeds</wicri:regionArea>
<wicri:noRegion>Leeds</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Newton Bishop, J" sort="Newton Bishop, J" uniqKey="Newton Bishop J" first="J" last="Newton-Bishop">J. Newton-Bishop</name>
<affiliation wicri:level="1"><nlm:affiliation>Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, Leeds, United Kingdom.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, Leeds</wicri:regionArea>
<wicri:noRegion>Leeds</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Williams, N M" sort="Williams, N M" uniqKey="Williams N" first="N M" last="Williams">N M Williams</name>
<affiliation wicri:level="1"><nlm:affiliation>Institute of Psychological Medicine and Clinical Neurosciences, Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, Cardiff University School of Medicine, Cardiff, United Kingdom.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Institute of Psychological Medicine and Clinical Neurosciences, Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, Cardiff University School of Medicine, Cardiff</wicri:regionArea>
<wicri:noRegion>Cardiff</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Morris, H R" sort="Morris, H R" uniqKey="Morris H" first="H R" last="Morris">H R Morris</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Clinical Neuroscience, UCL Institute of Neurology, London, United Kingdom. Electronic address: h.morris@ucl.ac.uk.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Clinical Neuroscience, UCL Institute of Neurology, 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">Neurobiology of aging</title>
<idno type="eISSN">1558-1497</idno>
<imprint><date when="2016" type="published">2016</date>
</imprint>
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<front><div type="abstract" xml:lang="en">A shared genetic susceptibility between cutaneous malignant melanoma (CMM) and Parkinson's disease (PD) has been suggested. We investigated this by assessing the contribution of rare variants in genes involved in CMM to PD risk. We studied rare variation across 29 CMM risk genes using high-quality genotype data in 6875 PD cases and 6065 controls and sought to replicate findings using whole-exome sequencing data from a second independent cohort totaling 1255 PD cases and 473 controls. No statistically significant enrichment of rare variants across all genes, per gene, or for any individual variant was detected in either cohort. There were nonsignificant trends toward different carrier frequencies between PD cases and controls, under different inheritance models, in the following CMM risk genes: BAP1, DCC, ERBB4, KIT, MAPK2, MITF, PTEN, and TP53. The very rare TYR p.V275F variant, which is a pathogenic allele for recessive albinism, was more common in PD cases than controls in 3 independent cohorts. Tyrosinase, encoded by TYR, is the rate-limiting enzyme for the production of neuromelanin, and has a role in the production of dopamine. These results suggest a possible role for another gene in the dopamine-biosynthetic pathway in susceptibility to neurodegenerative Parkinsonism, but further studies in larger PD cohorts are needed to accurately determine the role of these genes/variants in disease pathogenesis.</div>
</front>
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