DCAF4, a novel gene associated with leucocyte telomere length
Identifieur interne : 003285 ( Main/Exploration ); précédent : 003284; suivant : 003286DCAF4, a novel gene associated with leucocyte telomere length
Auteurs : Massimo Mangino [Royaume-Uni] ; Lene Christiansen [Danemark] ; Rivka Stone [États-Unis] ; Steven C. Hunt [États-Unis] ; Kent Horvath [États-Unis] ; Dan T A. Eisenberg [États-Unis] ; Masayuki Kimura [États-Unis] ; Inge Petersen [Danemark] ; Jeremy D. Kark [Israël] ; Utz Herbig [États-Unis] ; Alex P. Reiner [États-Unis] ; Athanase Benetos [France] ; Veryan Codd [Royaume-Uni] ; Dale R. Nyholt [Australie] ; Ronit Sinnreich [Israël] ; Kaare Christensen [Danemark] ; Hisham Nassar [Israël] ; Shih-Jen Hwang [États-Unis] ; Daniel Levy [États-Unis] ; Veronique Bataille [Royaume-Uni] ; Annette L. Fitzpatrick [États-Unis] ; Wei Chen [États-Unis] ; Gerald S. Berenson [États-Unis] ; Nilesh J. Samani [Royaume-Uni] ; Nicholas G. Martin [Australie] ; Sarah Tishkoff [États-Unis] ; Nicholas J. Schork [États-Unis] ; Kirsten Ohm Kyvik [Danemark] ; Christine Dalg Rd [Danemark] ; Timothy D. Spector [Royaume-Uni] ; Abraham Aviv [États-Unis]Source :
- Journal of Medical Genetics [ 0022-2593 ] ; 2015.
Descripteurs français
- KwdFr :
- Allèles, Facteurs de risque, Homéostasie des télomères (génétique), Humains, Leucocytes (cytologie), Mélanome (anatomopathologie), Mélanome (génétique), Mélanome (sang), Protéines de transport (biosynthèse), Protéines de transport (génétique), Protéines de transport (sang), Régulation de l'expression des gènes, Télomère (génétique), Étude d'association pangénomique.
- MESH :
- anatomopathologie : Mélanome.
- biosynthèse : Protéines de transport.
- cytologie : Leucocytes.
- génétique : Homéostasie des télomères, Mélanome, Protéines de transport, Télomère.
- sang : Mélanome, Protéines de transport.
- Allèles, Facteurs de risque, Humains, Régulation de l'expression des gènes, Étude d'association pangénomique.
English descriptors
- KwdEn :
- Alleles, Carrier Proteins (biosynthesis), Carrier Proteins (blood), Carrier Proteins (genetics), Gene Expression Regulation, Genome-Wide Association Study, Humans, Leukocytes (cytology), Melanoma (blood), Melanoma (genetics), Melanoma (pathology), Risk Factors, Telomere (genetics), Telomere Homeostasis (genetics).
- MESH :
- chemical , biosynthesis : Carrier Proteins.
- chemical , blood : Carrier Proteins.
- chemical , genetics : Carrier Proteins.
- blood : Melanoma.
- cytology : Leukocytes.
- genetics : Melanoma, Telomere, Telomere Homeostasis.
- pathology : Melanoma.
- Alleles, Gene Expression Regulation, Genome-Wide Association Study, Humans, Risk Factors.
Abstract
Leucocyte telomere length (LTL), which is fashioned by multiple genes, has been linked to a host of human diseases, including sporadic melanoma. A number of genes associated with LTL have already been identified through genome-wide association studies. The main aim of this study was to establish whether
Genome-wide association (GWA) meta-analysis and de novo genotyping of 20 022 individuals revealed a novel association (p=6.4×10−10) between LTL and rs2535913, which lies within
We uncovered a new locus associated with LTL in the general population. We also provided preliminary findings that suggest a link of LTL through genetic mechanisms with UVR and melanoma in the general population.
Url:
DOI: 10.1136/jmedgenet-2014-102681
PubMed: 25624462
PubMed Central: 4345921
Affiliations:
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Le document en format XML
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, a novel gene associated with leucocyte telomere length</title>
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<author><name sortKey="Kimura, Masayuki" sort="Kimura, Masayuki" uniqKey="Kimura M" first="Masayuki" last="Kimura">Masayuki Kimura</name>
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<author><name sortKey="Petersen, Inge" sort="Petersen, Inge" uniqKey="Petersen I" first="Inge" last="Petersen">Inge Petersen</name>
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<country xml:lang="fr">États-Unis</country>
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<author><name sortKey="Benetos, Athanase" sort="Benetos, Athanase" uniqKey="Benetos A" first="Athanase" last="Benetos">Athanase Benetos</name>
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</nlm:aff>
<country xml:lang="fr">France</country>
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<author><name sortKey="Codd, Veryan" sort="Codd, Veryan" uniqKey="Codd V" first="Veryan" last="Codd">Veryan Codd</name>
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</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
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<affiliation wicri:level="1"><nlm:aff id="af14"><institution>National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital</institution>
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<author><name sortKey="Nyholt, Dale R" sort="Nyholt, Dale R" uniqKey="Nyholt D" first="Dale R" last="Nyholt">Dale R. Nyholt</name>
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<author><name sortKey="Sinnreich, Ronit" sort="Sinnreich, Ronit" uniqKey="Sinnreich R" first="Ronit" last="Sinnreich">Ronit Sinnreich</name>
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<author><name sortKey="Christensen, Kaare" sort="Christensen, Kaare" uniqKey="Christensen K" first="Kaare" last="Christensen">Kaare Christensen</name>
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<country xml:lang="fr">Danemark</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<affiliation wicri:level="1"><nlm:aff id="af4"><addr-line>Department of Clinical Genetics, and Department of Clinical Biochemistry and Pharmacology</addr-line>
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,<addr-line>Odense</addr-line>
,<country>Denmark</country>
</nlm:aff>
<country xml:lang="fr">Danemark</country>
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<author><name sortKey="Nassar, Hisham" sort="Nassar, Hisham" uniqKey="Nassar H" first="Hisham" last="Nassar">Hisham Nassar</name>
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</nlm:aff>
<country xml:lang="fr">Israël</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Hwang, Shih Jen" sort="Hwang, Shih Jen" uniqKey="Hwang S" first="Shih-Jen" last="Hwang">Shih-Jen Hwang</name>
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</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<affiliation wicri:level="1"><nlm:aff id="af18"><institution>The Framingham Heart Study</institution>
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<country xml:lang="fr">États-Unis</country>
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<author><name sortKey="Levy, Daniel" sort="Levy, Daniel" uniqKey="Levy D" first="Daniel" last="Levy">Daniel Levy</name>
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</nlm:aff>
<country xml:lang="fr">États-Unis</country>
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<affiliation wicri:level="1"><nlm:aff id="af18"><institution>The Framingham Heart Study</institution>
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</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Bataille, Veronique" sort="Bataille, Veronique" uniqKey="Bataille V" first="Veronique" last="Bataille">Veronique Bataille</name>
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,<addr-line>London</addr-line>
,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af19"><addr-line>Department of Dermatology</addr-line>
,<institution>West Herts NHS Trust</institution>
,<addr-line>Herts</addr-line>
,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Fitzpatrick, Annette L" sort="Fitzpatrick, Annette L" uniqKey="Fitzpatrick A" first="Annette L" last="Fitzpatrick">Annette L. Fitzpatrick</name>
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,<institution>University of Washington</institution>
,<addr-line>Seattle, Washington</addr-line>
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</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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</author>
<author><name sortKey="Chen, Wei" sort="Chen, Wei" uniqKey="Chen W" first="Wei" last="Chen">Wei Chen</name>
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,<institution>Tulane University</institution>
,<addr-line>New Orleans, Louisiana</addr-line>
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</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Berenson, Gerald S" sort="Berenson, Gerald S" uniqKey="Berenson G" first="Gerald S" last="Berenson">Gerald S. Berenson</name>
<affiliation wicri:level="1"><nlm:aff id="af20"><addr-line>Center for Cardiovascular Health</addr-line>
,<institution>Tulane University</institution>
,<addr-line>New Orleans, Louisiana</addr-line>
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</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Samani, Nilesh J" sort="Samani, Nilesh J" uniqKey="Samani N" first="Nilesh J" last="Samani">Nilesh J. Samani</name>
<affiliation wicri:level="1"><nlm:aff id="af13"><addr-line>Department of Cardiovascular Sciences</addr-line>
,<institution>University of Leicester</institution>
,<addr-line>Leicester</addr-line>
,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af14"><institution>National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital</institution>
,<addr-line>Leicester</addr-line>
,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Martin, Nicholas G" sort="Martin, Nicholas G" uniqKey="Martin N" first="Nicholas G" last="Martin">Nicholas G. Martin</name>
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,<addr-line>Brisbane</addr-line>
,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Tishkoff, Sarah" sort="Tishkoff, Sarah" uniqKey="Tishkoff S" first="Sarah" last="Tishkoff">Sarah Tishkoff</name>
<affiliation wicri:level="1"><nlm:aff id="af21"><addr-line>Department of Genetics</addr-line>
,<institution>University of Pennsylvania</institution>
,<addr-line>Philadelphia, Pennsylvania</addr-line>
,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Schork, Nicholas J" sort="Schork, Nicholas J" uniqKey="Schork N" first="Nicholas J" last="Schork">Nicholas J. Schork</name>
<affiliation wicri:level="1"><nlm:aff id="af22"><addr-line>Department of Molecular and Experimental Medicine</addr-line>
,<institution>The Scripps Research Institute</institution>
,<addr-line>San Diego, California</addr-line>
,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Kyvik, Kirsten Ohm" sort="Kyvik, Kirsten Ohm" uniqKey="Kyvik K" first="Kirsten Ohm" last="Kyvik">Kirsten Ohm Kyvik</name>
<affiliation wicri:level="1"><nlm:aff id="af3"><addr-line>Epidemiology Unit</addr-line>
,<institution>The Danish Aging Research Center and The Danish Twin Registry, Institute of Public Health, University of Southern Denmark</institution>
,<addr-line>Odense</addr-line>
,<country>Denmark</country>
</nlm:aff>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af23"><institution>Institute of Regional Health Services Research, University of Southern Denmark</institution>
,<addr-line>Odense</addr-line>
,<country>Denmark</country>
</nlm:aff>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af24"><institution>Odense Patient data Explorative Network (OPEN), Odense University Hospital</institution>
,<addr-line>Odense</addr-line>
,<country>Denmark</country>
</nlm:aff>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Dalg Rd, Christine" sort="Dalg Rd, Christine" uniqKey="Dalg Rd C" first="Christine" last="Dalg Rd">Christine Dalg Rd</name>
<affiliation wicri:level="1"><nlm:aff id="af25"><institution>Institute of Public Health, Environmental Medicine, University of Southern Denmark</institution>
,<addr-line>Odense</addr-line>
,<country>Denmark</country>
</nlm:aff>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Spector, Timothy D" sort="Spector, Timothy D" uniqKey="Spector T" first="Timothy D" last="Spector">Timothy D. Spector</name>
<affiliation wicri:level="1"><nlm:aff id="af1"><addr-line>Department of Twin Research and Genetic Epidemiology</addr-line>
,<institution>King's College London</institution>
,<addr-line>London</addr-line>
,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Aviv, Abraham" sort="Aviv, Abraham" uniqKey="Aviv A" first="Abraham" last="Aviv">Abraham Aviv</name>
<affiliation wicri:level="1"><nlm:aff id="af5"><institution>Center of Human Development and Aging, Rutgers, The State University of New Jersey, New Jersey Medical School</institution>
,<addr-line>Newark, New Jersey</addr-line>
,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">25624462</idno>
<idno type="pmc">4345921</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4345921</idno>
<idno type="RBID">PMC:4345921</idno>
<idno type="doi">10.1136/jmedgenet-2014-102681</idno>
<date when="2015">2015</date>
<idno type="wicri:Area/Pmc/Corpus">000557</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000557</idno>
<idno type="wicri:Area/Pmc/Curation">000557</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000557</idno>
<idno type="wicri:Area/Pmc/Checkpoint">001251</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">001251</idno>
<idno type="wicri:source">PubMed</idno>
<idno type="wicri:Area/PubMed/Corpus">002F77</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002F77</idno>
<idno type="wicri:Area/PubMed/Curation">002E98</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">002E98</idno>
<idno type="wicri:Area/PubMed/Checkpoint">002E98</idno>
<idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">002E98</idno>
<idno type="wicri:Area/Ncbi/Merge">002202</idno>
<idno type="wicri:Area/Ncbi/Curation">002202</idno>
<idno type="wicri:Area/Ncbi/Checkpoint">002202</idno>
<idno type="wicri:Area/Main/Merge">003286</idno>
<idno type="wicri:Area/Main/Curation">003285</idno>
<idno type="wicri:Area/Main/Exploration">003285</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main"><italic>DCAF4</italic>
, a novel gene associated with leucocyte telomere length</title>
<author><name sortKey="Mangino, Massimo" sort="Mangino, Massimo" uniqKey="Mangino M" first="Massimo" last="Mangino">Massimo Mangino</name>
<affiliation wicri:level="1"><nlm:aff id="af1"><addr-line>Department of Twin Research and Genetic Epidemiology</addr-line>
,<institution>King's College London</institution>
,<addr-line>London</addr-line>
,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af2"><institution>National Institute for Health Research (NIHR) Biomedical Research Centre at Guy's and St. Thomas’ Foundation Trust</institution>
,<addr-line>London</addr-line>
,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Christiansen, Lene" sort="Christiansen, Lene" uniqKey="Christiansen L" first="Lene" last="Christiansen">Lene Christiansen</name>
<affiliation wicri:level="1"><nlm:aff id="af3"><addr-line>Epidemiology Unit</addr-line>
,<institution>The Danish Aging Research Center and The Danish Twin Registry, Institute of Public Health, University of Southern Denmark</institution>
,<addr-line>Odense</addr-line>
,<country>Denmark</country>
</nlm:aff>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af4"><addr-line>Department of Clinical Genetics, and Department of Clinical Biochemistry and Pharmacology</addr-line>
,<institution>Odense University Hospital</institution>
,<addr-line>Odense</addr-line>
,<country>Denmark</country>
</nlm:aff>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Stone, Rivka" sort="Stone, Rivka" uniqKey="Stone R" first="Rivka" last="Stone">Rivka Stone</name>
<affiliation wicri:level="1"><nlm:aff id="af5"><institution>Center of Human Development and Aging, Rutgers, The State University of New Jersey, New Jersey Medical School</institution>
,<addr-line>Newark, New Jersey</addr-line>
,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Hunt, Steven C" sort="Hunt, Steven C" uniqKey="Hunt S" first="Steven C" last="Hunt">Steven C. Hunt</name>
<affiliation wicri:level="1"><nlm:aff id="af6"><addr-line>Cardiovascular Genetics Division, Department of Medicine</addr-line>
,<institution>University of Utah</institution>
,<addr-line>Salt Lake City, Utah</addr-line>
,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Horvath, Kent" sort="Horvath, Kent" uniqKey="Horvath K" first="Kent" last="Horvath">Kent Horvath</name>
<affiliation wicri:level="1"><nlm:aff id="af5"><institution>Center of Human Development and Aging, Rutgers, The State University of New Jersey, New Jersey Medical School</institution>
,<addr-line>Newark, New Jersey</addr-line>
,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Eisenberg, Dan T A" sort="Eisenberg, Dan T A" uniqKey="Eisenberg D" first="Dan T A" last="Eisenberg">Dan T A. Eisenberg</name>
<affiliation wicri:level="1"><nlm:aff id="af7"><addr-line>Department of Anthropology</addr-line>
,<institution>University of Washington</institution>
,<addr-line>Seattle, Washington</addr-line>
,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af8"><institution>Center for Studies in Demography and Ecology, University of Washington</institution>
,<addr-line>Seattle, Washington</addr-line>
,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Kimura, Masayuki" sort="Kimura, Masayuki" uniqKey="Kimura M" first="Masayuki" last="Kimura">Masayuki Kimura</name>
<affiliation wicri:level="1"><nlm:aff id="af5"><institution>Center of Human Development and Aging, Rutgers, The State University of New Jersey, New Jersey Medical School</institution>
,<addr-line>Newark, New Jersey</addr-line>
,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Petersen, Inge" sort="Petersen, Inge" uniqKey="Petersen I" first="Inge" last="Petersen">Inge Petersen</name>
<affiliation wicri:level="1"><nlm:aff id="af3"><addr-line>Epidemiology Unit</addr-line>
,<institution>The Danish Aging Research Center and The Danish Twin Registry, Institute of Public Health, University of Southern Denmark</institution>
,<addr-line>Odense</addr-line>
,<country>Denmark</country>
</nlm:aff>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Kark, Jeremy D" sort="Kark, Jeremy D" uniqKey="Kark J" first="Jeremy D" last="Kark">Jeremy D. Kark</name>
<affiliation wicri:level="1"><nlm:aff id="af9"><addr-line>Epidemiology Unit</addr-line>
,<institution>Hebrew University-Hadassah School of Public Health and Community Medicine</institution>
,<addr-line>Jerusalem</addr-line>
,<country>Israel</country>
</nlm:aff>
<country xml:lang="fr">Israël</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Herbig, Utz" sort="Herbig, Utz" uniqKey="Herbig U" first="Utz" last="Herbig">Utz Herbig</name>
<affiliation wicri:level="1"><nlm:aff id="af5"><institution>Center of Human Development and Aging, Rutgers, The State University of New Jersey, New Jersey Medical School</institution>
,<addr-line>Newark, New Jersey</addr-line>
,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Reiner, Alex P" sort="Reiner, Alex P" uniqKey="Reiner A" first="Alex P" last="Reiner">Alex P. Reiner</name>
<affiliation wicri:level="1"><nlm:aff id="af10"><addr-line>Department of Epidemiology</addr-line>
,<institution>University of Washington</institution>
,<addr-line>Seattle, Washington</addr-line>
,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af11"><addr-line>Public Health Sciences Division</addr-line>
,<institution>Fred Hutchinson Cancer Research Center</institution>
,<addr-line>Seattle, Washington</addr-line>
,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Benetos, Athanase" sort="Benetos, Athanase" uniqKey="Benetos A" first="Athanase" last="Benetos">Athanase Benetos</name>
<affiliation wicri:level="1"><nlm:aff id="af12"><addr-line>Department of Geriatrics</addr-line>
,<institution>Universite de Lorraine INSERM U961</institution>
,<addr-line>Nancy</addr-line>
,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Codd, Veryan" sort="Codd, Veryan" uniqKey="Codd V" first="Veryan" last="Codd">Veryan Codd</name>
<affiliation wicri:level="1"><nlm:aff id="af13"><addr-line>Department of Cardiovascular Sciences</addr-line>
,<institution>University of Leicester</institution>
,<addr-line>Leicester</addr-line>
,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af14"><institution>National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital</institution>
,<addr-line>Leicester</addr-line>
,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Nyholt, Dale R" sort="Nyholt, Dale R" uniqKey="Nyholt D" first="Dale R" last="Nyholt">Dale R. Nyholt</name>
<affiliation wicri:level="1"><nlm:aff id="af15"><institution>QIMR Berghofer Medical Research Institute</institution>
,<addr-line>Brisbane</addr-line>
,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Sinnreich, Ronit" sort="Sinnreich, Ronit" uniqKey="Sinnreich R" first="Ronit" last="Sinnreich">Ronit Sinnreich</name>
<affiliation wicri:level="1"><nlm:aff id="af9"><addr-line>Epidemiology Unit</addr-line>
,<institution>Hebrew University-Hadassah School of Public Health and Community Medicine</institution>
,<addr-line>Jerusalem</addr-line>
,<country>Israel</country>
</nlm:aff>
<country xml:lang="fr">Israël</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Christensen, Kaare" sort="Christensen, Kaare" uniqKey="Christensen K" first="Kaare" last="Christensen">Kaare Christensen</name>
<affiliation wicri:level="1"><nlm:aff id="af3"><addr-line>Epidemiology Unit</addr-line>
,<institution>The Danish Aging Research Center and The Danish Twin Registry, Institute of Public Health, University of Southern Denmark</institution>
,<addr-line>Odense</addr-line>
,<country>Denmark</country>
</nlm:aff>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af4"><addr-line>Department of Clinical Genetics, and Department of Clinical Biochemistry and Pharmacology</addr-line>
,<institution>Odense University Hospital</institution>
,<addr-line>Odense</addr-line>
,<country>Denmark</country>
</nlm:aff>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Nassar, Hisham" sort="Nassar, Hisham" uniqKey="Nassar H" first="Hisham" last="Nassar">Hisham Nassar</name>
<affiliation wicri:level="1"><nlm:aff id="af16"><addr-line>Department of Cardiology</addr-line>
,<institution>Hadassah University Medical Center</institution>
,<addr-line>Jerusalem</addr-line>
,<country>Israel</country>
</nlm:aff>
<country xml:lang="fr">Israël</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Hwang, Shih Jen" sort="Hwang, Shih Jen" uniqKey="Hwang S" first="Shih-Jen" last="Hwang">Shih-Jen Hwang</name>
<affiliation wicri:level="1"><nlm:aff id="af17"><institution>Population Sciences Branch of the National Heart, Lung and Blood Institute</institution>
,<addr-line>Bethesda, Maryland</addr-line>
,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af18"><institution>The Framingham Heart Study</institution>
,<addr-line>Framingham, Massachusetts</addr-line>
,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Levy, Daniel" sort="Levy, Daniel" uniqKey="Levy D" first="Daniel" last="Levy">Daniel Levy</name>
<affiliation wicri:level="1"><nlm:aff id="af17"><institution>Population Sciences Branch of the National Heart, Lung and Blood Institute</institution>
,<addr-line>Bethesda, Maryland</addr-line>
,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af18"><institution>The Framingham Heart Study</institution>
,<addr-line>Framingham, Massachusetts</addr-line>
,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bataille, Veronique" sort="Bataille, Veronique" uniqKey="Bataille V" first="Veronique" last="Bataille">Veronique Bataille</name>
<affiliation wicri:level="1"><nlm:aff id="af1"><addr-line>Department of Twin Research and Genetic Epidemiology</addr-line>
,<institution>King's College London</institution>
,<addr-line>London</addr-line>
,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af19"><addr-line>Department of Dermatology</addr-line>
,<institution>West Herts NHS Trust</institution>
,<addr-line>Herts</addr-line>
,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Fitzpatrick, Annette L" sort="Fitzpatrick, Annette L" uniqKey="Fitzpatrick A" first="Annette L" last="Fitzpatrick">Annette L. Fitzpatrick</name>
<affiliation wicri:level="1"><nlm:aff id="af10"><addr-line>Department of Epidemiology</addr-line>
,<institution>University of Washington</institution>
,<addr-line>Seattle, Washington</addr-line>
,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Chen, Wei" sort="Chen, Wei" uniqKey="Chen W" first="Wei" last="Chen">Wei Chen</name>
<affiliation wicri:level="1"><nlm:aff id="af20"><addr-line>Center for Cardiovascular Health</addr-line>
,<institution>Tulane University</institution>
,<addr-line>New Orleans, Louisiana</addr-line>
,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Berenson, Gerald S" sort="Berenson, Gerald S" uniqKey="Berenson G" first="Gerald S" last="Berenson">Gerald S. Berenson</name>
<affiliation wicri:level="1"><nlm:aff id="af20"><addr-line>Center for Cardiovascular Health</addr-line>
,<institution>Tulane University</institution>
,<addr-line>New Orleans, Louisiana</addr-line>
,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Samani, Nilesh J" sort="Samani, Nilesh J" uniqKey="Samani N" first="Nilesh J" last="Samani">Nilesh J. Samani</name>
<affiliation wicri:level="1"><nlm:aff id="af13"><addr-line>Department of Cardiovascular Sciences</addr-line>
,<institution>University of Leicester</institution>
,<addr-line>Leicester</addr-line>
,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af14"><institution>National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital</institution>
,<addr-line>Leicester</addr-line>
,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</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="af15"><institution>QIMR Berghofer Medical Research Institute</institution>
,<addr-line>Brisbane</addr-line>
,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Tishkoff, Sarah" sort="Tishkoff, Sarah" uniqKey="Tishkoff S" first="Sarah" last="Tishkoff">Sarah Tishkoff</name>
<affiliation wicri:level="1"><nlm:aff id="af21"><addr-line>Department of Genetics</addr-line>
,<institution>University of Pennsylvania</institution>
,<addr-line>Philadelphia, Pennsylvania</addr-line>
,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Schork, Nicholas J" sort="Schork, Nicholas J" uniqKey="Schork N" first="Nicholas J" last="Schork">Nicholas J. Schork</name>
<affiliation wicri:level="1"><nlm:aff id="af22"><addr-line>Department of Molecular and Experimental Medicine</addr-line>
,<institution>The Scripps Research Institute</institution>
,<addr-line>San Diego, California</addr-line>
,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Kyvik, Kirsten Ohm" sort="Kyvik, Kirsten Ohm" uniqKey="Kyvik K" first="Kirsten Ohm" last="Kyvik">Kirsten Ohm Kyvik</name>
<affiliation wicri:level="1"><nlm:aff id="af3"><addr-line>Epidemiology Unit</addr-line>
,<institution>The Danish Aging Research Center and The Danish Twin Registry, Institute of Public Health, University of Southern Denmark</institution>
,<addr-line>Odense</addr-line>
,<country>Denmark</country>
</nlm:aff>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af23"><institution>Institute of Regional Health Services Research, University of Southern Denmark</institution>
,<addr-line>Odense</addr-line>
,<country>Denmark</country>
</nlm:aff>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af24"><institution>Odense Patient data Explorative Network (OPEN), Odense University Hospital</institution>
,<addr-line>Odense</addr-line>
,<country>Denmark</country>
</nlm:aff>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Dalg Rd, Christine" sort="Dalg Rd, Christine" uniqKey="Dalg Rd C" first="Christine" last="Dalg Rd">Christine Dalg Rd</name>
<affiliation wicri:level="1"><nlm:aff id="af25"><institution>Institute of Public Health, Environmental Medicine, University of Southern Denmark</institution>
,<addr-line>Odense</addr-line>
,<country>Denmark</country>
</nlm:aff>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Spector, Timothy D" sort="Spector, Timothy D" uniqKey="Spector T" first="Timothy D" last="Spector">Timothy D. Spector</name>
<affiliation wicri:level="1"><nlm:aff id="af1"><addr-line>Department of Twin Research and Genetic Epidemiology</addr-line>
,<institution>King's College London</institution>
,<addr-line>London</addr-line>
,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Aviv, Abraham" sort="Aviv, Abraham" uniqKey="Aviv A" first="Abraham" last="Aviv">Abraham Aviv</name>
<affiliation wicri:level="1"><nlm:aff id="af5"><institution>Center of Human Development and Aging, Rutgers, The State University of New Jersey, New Jersey Medical School</institution>
,<addr-line>Newark, New Jersey</addr-line>
,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series><title level="j">Journal of Medical Genetics</title>
<idno type="ISSN">0022-2593</idno>
<idno type="eISSN">1468-6244</idno>
<imprint><date when="2015">2015</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Alleles</term>
<term>Carrier Proteins (biosynthesis)</term>
<term>Carrier Proteins (blood)</term>
<term>Carrier Proteins (genetics)</term>
<term>Gene Expression Regulation</term>
<term>Genome-Wide Association Study</term>
<term>Humans</term>
<term>Leukocytes (cytology)</term>
<term>Melanoma (blood)</term>
<term>Melanoma (genetics)</term>
<term>Melanoma (pathology)</term>
<term>Risk Factors</term>
<term>Telomere (genetics)</term>
<term>Telomere Homeostasis (genetics)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Allèles</term>
<term>Facteurs de risque</term>
<term>Homéostasie des télomères (génétique)</term>
<term>Humains</term>
<term>Leucocytes (cytologie)</term>
<term>Mélanome (anatomopathologie)</term>
<term>Mélanome (génétique)</term>
<term>Mélanome (sang)</term>
<term>Protéines de transport (biosynthèse)</term>
<term>Protéines de transport (génétique)</term>
<term>Protéines de transport (sang)</term>
<term>Régulation de l'expression des gènes</term>
<term>Télomère (génétique)</term>
<term>Étude d'association pangénomique</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Carrier Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Carrier Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Carrier Proteins</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Mélanome</term>
</keywords>
<keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Protéines de transport</term>
</keywords>
<keywords scheme="MESH" qualifier="blood" xml:lang="en"><term>Melanoma</term>
</keywords>
<keywords scheme="MESH" qualifier="cytologie" xml:lang="fr"><term>Leucocytes</term>
</keywords>
<keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Leukocytes</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Melanoma</term>
<term>Telomere</term>
<term>Telomere Homeostasis</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Homéostasie des télomères</term>
<term>Mélanome</term>
<term>Protéines de transport</term>
<term>Télomère</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Melanoma</term>
</keywords>
<keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>Mélanome</term>
<term>Protéines de transport</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Alleles</term>
<term>Gene Expression Regulation</term>
<term>Genome-Wide Association Study</term>
<term>Humans</term>
<term>Risk Factors</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Allèles</term>
<term>Facteurs de risque</term>
<term>Humains</term>
<term>Régulation de l'expression des gènes</term>
<term>Étude d'association pangénomique</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><sec><title>Background</title>
<p>Leucocyte telomere length (LTL), which is fashioned by multiple genes, has been linked to a host of human diseases, including sporadic melanoma. A number of genes associated with LTL have already been identified through genome-wide association studies. The main aim of this study was to establish whether <italic>DCAF4</italic>
(DDB1 and CUL4-associated factor 4) is associated with LTL. In addition, using ingenuity pathway analysis (IPA), we examined whether LTL-associated genes in the general population might partially explain the inherently longer LTL in patients with sporadic melanoma, the risk for which is increased with ultraviolet radiation (UVR).</p>
</sec>
<sec><title>Results</title>
<p>Genome-wide association (GWA) meta-analysis and de novo genotyping of 20 022 individuals revealed a novel association (p=6.4×10<sup>−10</sup>
) between LTL and rs2535913, which lies within <italic>DCAF4</italic>
. Notably, eQTL analysis showed that rs2535913 is associated with decline in <italic>DCAF4</italic>
expressions in both lymphoblastoid cells and sun-exposed skin (p=4.1×10<sup>−3</sup>
and 2×10<sup>−3</sup>
, respectively). Moreover, IPA revealed that LTL-associated genes, derived from GWA meta-analysis (N=9190), are over-represented among genes engaged in melanoma pathways. Meeting increasingly stringent p value thresholds (p<0.05, <0.01, <0.005, <0.001) in the LTL-GWA meta-analysis, these genes were jointly over-represented for melanoma at p values ranging from 1.97×10<sup>−169</sup>
to 3.42×10<sup>−24</sup>
.</p>
</sec>
<sec><title>Conclusions</title>
<p>We uncovered a new locus associated with LTL in the general population. We also provided preliminary findings that suggest a link of LTL through genetic mechanisms with UVR and melanoma in the general population.</p>
</sec>
</div>
</front>
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</TEI>
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<li>Danemark</li>
<li>France</li>
<li>Israël</li>
<li>Royaume-Uni</li>
<li>États-Unis</li>
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