DCAF4, a novel gene associated with leucocyte telomere length
Identifieur interne : 001251 ( Pmc/Checkpoint ); précédent : 001250; suivant : 001252DCAF4, 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.
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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Links to Exploration step
PMC:4345921Le document en format XML
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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></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></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></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. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">J Med Genet</journal-id><journal-id journal-id-type="iso-abbrev">J. Med. Genet</journal-id><journal-id journal-id-type="hwp">jmedgenet</journal-id><journal-id journal-id-type="publisher-id">jmg</journal-id><journal-title-group><journal-title>Journal of Medical Genetics</journal-title></journal-title-group><issn pub-type="ppub">0022-2593</issn><issn pub-type="epub">1468-6244</issn><publisher><publisher-name>BMJ Publishing Group</publisher-name><publisher-loc>BMA House, Tavistock Square, London, WC1H 9JR</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">25624462</article-id><article-id pub-id-type="pmc">4345921</article-id><article-id pub-id-type="publisher-id">jmedgenet-2014-102681</article-id><article-id pub-id-type="doi">10.1136/jmedgenet-2014-102681</article-id><article-categories><subj-group subj-group-type="hwp-journal-coll"><subject>1506</subject></subj-group><subj-group subj-group-type="heading"><subject>Genome-Wide Studies</subject></subj-group><series-title>Original article</series-title></article-categories><title-group><article-title><italic>DCAF4</italic>, a novel gene associated with leucocyte telomere length</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Mangino</surname><given-names>Massimo</given-names></name><xref ref-type="aff" rid="af1">1</xref><xref ref-type="aff" rid="af2">2</xref></contrib><contrib contrib-type="author"><name><surname>Christiansen</surname><given-names>Lene</given-names></name><xref ref-type="aff" rid="af3">3</xref><xref ref-type="aff" rid="af4">4</xref></contrib><contrib contrib-type="author"><name><surname>Stone</surname><given-names>Rivka</given-names></name><xref ref-type="aff" rid="af5">5</xref></contrib><contrib contrib-type="author"><name><surname>Hunt</surname><given-names>Steven C</given-names></name><xref ref-type="aff" rid="af6">6</xref></contrib><contrib contrib-type="author"><name><surname>Horvath</surname><given-names>Kent</given-names></name><xref ref-type="aff" rid="af5">5</xref></contrib><contrib contrib-type="author"><name><surname>Eisenberg</surname><given-names>Dan T A</given-names></name><xref ref-type="aff" rid="af7">7</xref><xref ref-type="aff" rid="af8">8</xref></contrib><contrib contrib-type="author"><name><surname>Kimura</surname><given-names>Masayuki</given-names></name><xref ref-type="aff" rid="af5">5</xref></contrib><contrib contrib-type="author"><name><surname>Petersen</surname><given-names>Inge</given-names></name><xref ref-type="aff" rid="af3">3</xref></contrib><contrib contrib-type="author"><name><surname>Kark</surname><given-names>Jeremy D</given-names></name><xref ref-type="aff" rid="af9">9</xref></contrib><contrib contrib-type="author"><name><surname>Herbig</surname><given-names>Utz</given-names></name><xref ref-type="aff" rid="af5">5</xref></contrib><contrib contrib-type="author"><name><surname>Reiner</surname><given-names>Alex P</given-names></name><xref ref-type="aff" rid="af10">10</xref><xref ref-type="aff" rid="af11">11</xref></contrib><contrib contrib-type="author"><name><surname>Benetos</surname><given-names>Athanase</given-names></name><xref ref-type="aff" rid="af12">12</xref></contrib><contrib contrib-type="author"><name><surname>Codd</surname><given-names>Veryan</given-names></name><xref ref-type="aff" rid="af13">13</xref><xref ref-type="aff" rid="af14">14</xref></contrib><contrib contrib-type="author"><name><surname>Nyholt</surname><given-names>Dale R</given-names></name><xref ref-type="aff" rid="af15">15</xref></contrib><contrib contrib-type="author"><name><surname>Sinnreich</surname><given-names>Ronit</given-names></name><xref ref-type="aff" rid="af9">9</xref></contrib><contrib contrib-type="author"><name><surname>Christensen</surname><given-names>Kaare</given-names></name><xref ref-type="aff" rid="af3">3</xref><xref ref-type="aff" rid="af4">4</xref></contrib><contrib contrib-type="author"><name><surname>Nassar</surname><given-names>Hisham</given-names></name><xref ref-type="aff" rid="af16">16</xref></contrib><contrib contrib-type="author"><name><surname>Hwang</surname><given-names>Shih-Jen</given-names></name><xref ref-type="aff" rid="af17">17</xref><xref ref-type="aff" rid="af18">18</xref></contrib><contrib contrib-type="author"><name><surname>Levy</surname><given-names>Daniel</given-names></name><xref ref-type="aff" rid="af17">17</xref><xref ref-type="aff" rid="af18">18</xref></contrib><contrib contrib-type="author"><name><surname>Bataille</surname><given-names>Veronique</given-names></name><xref ref-type="aff" rid="af1">1</xref><xref ref-type="aff" rid="af19">19</xref></contrib><contrib contrib-type="author"><name><surname>Fitzpatrick</surname><given-names>Annette L</given-names></name><xref ref-type="aff" rid="af10">10</xref></contrib><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Wei</given-names></name><xref ref-type="aff" rid="af20">20</xref></contrib><contrib contrib-type="author"><name><surname>Berenson</surname><given-names>Gerald S</given-names></name><xref ref-type="aff" rid="af20">20</xref></contrib><contrib contrib-type="author"><name><surname>Samani</surname><given-names>Nilesh J</given-names></name><xref ref-type="aff" rid="af13">13</xref><xref ref-type="aff" rid="af14">14</xref></contrib><contrib contrib-type="author"><name><surname>Martin</surname><given-names>Nicholas G</given-names></name><xref ref-type="aff" rid="af15">15</xref></contrib><contrib contrib-type="author"><name><surname>Tishkoff</surname><given-names>Sarah</given-names></name><xref ref-type="aff" rid="af21">21</xref></contrib><contrib contrib-type="author"><name><surname>Schork</surname><given-names>Nicholas J</given-names></name><xref ref-type="aff" rid="af22">22</xref></contrib><contrib contrib-type="author"><name><surname>Kyvik</surname><given-names>Kirsten Ohm</given-names></name><xref ref-type="aff" rid="af3">3</xref><xref ref-type="aff" rid="af23">23</xref><xref ref-type="aff" rid="af24">24</xref></contrib><contrib contrib-type="author"><name><surname>Dalgård</surname><given-names>Christine</given-names></name><xref ref-type="aff" rid="af25">25</xref></contrib><contrib contrib-type="author"><name><surname>Spector</surname><given-names>Timothy D</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Aviv</surname><given-names>Abraham</given-names></name><xref ref-type="aff" rid="af5">5</xref></contrib></contrib-group><aff id="af1"><label>1</label><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></aff><aff id="af2"><label>2</label><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></aff><aff id="af3"><label>3</label><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></aff><aff id="af4"><label>4</label><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></aff><aff id="af5"><label>5</label><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></aff><aff id="af6"><label>6</label><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></aff><aff id="af7"><label>7</label><addr-line>Department of Anthropology</addr-line>,<institution>University of Washington</institution>,<addr-line>Seattle, Washington</addr-line>,<country>USA</country></aff><aff id="af8"><label>8</label><institution>Center for Studies in Demography and Ecology, University of Washington</institution>,<addr-line>Seattle, Washington</addr-line>,<country>USA</country></aff><aff id="af9"><label>9</label><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></aff><aff id="af10"><label>10</label><addr-line>Department of Epidemiology</addr-line>,<institution>University of Washington</institution>,<addr-line>Seattle, Washington</addr-line>,<country>USA</country></aff><aff id="af11"><label>11</label><addr-line>Public Health Sciences Division</addr-line>,<institution>Fred Hutchinson Cancer Research Center</institution>,<addr-line>Seattle, Washington</addr-line>,<country>USA</country></aff><aff id="af12"><label>12</label><addr-line>Department of Geriatrics</addr-line>,<institution>Universite de Lorraine INSERM U961</institution>,<addr-line>Nancy</addr-line>,<country>France</country></aff><aff id="af13"><label>13</label><addr-line>Department of Cardiovascular Sciences</addr-line>,<institution>University of Leicester</institution>,<addr-line>Leicester</addr-line>,<country>UK</country></aff><aff id="af14"><label>14</label><institution>National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital</institution>,<addr-line>Leicester</addr-line>,<country>UK</country></aff><aff id="af15"><label>15</label><institution>QIMR Berghofer Medical Research Institute</institution>,<addr-line>Brisbane</addr-line>,<country>Australia</country></aff><aff id="af16"><label>16</label><addr-line>Department of Cardiology</addr-line>,<institution>Hadassah University Medical Center</institution>,<addr-line>Jerusalem</addr-line>,<country>Israel</country></aff><aff id="af17"><label>17</label><institution>Population Sciences Branch of the National Heart, Lung and Blood Institute</institution>,<addr-line>Bethesda, Maryland</addr-line>,<country>USA</country></aff><aff id="af18"><label>18</label><institution>The Framingham Heart Study</institution>,<addr-line>Framingham, Massachusetts</addr-line>,<country>USA</country></aff><aff id="af19"><label>19</label><addr-line>Department of Dermatology</addr-line>,<institution>West Herts NHS Trust</institution>,<addr-line>Herts</addr-line>,<country>UK</country></aff><aff id="af20"><label>20</label><addr-line>Center for Cardiovascular Health</addr-line>,<institution>Tulane University</institution>,<addr-line>New Orleans, Louisiana</addr-line>,<country>USA</country></aff><aff id="af21"><label>21</label><addr-line>Department of Genetics</addr-line>,<institution>University of Pennsylvania</institution>,<addr-line>Philadelphia, Pennsylvania</addr-line>,<country>USA</country></aff><aff id="af22"><label>22</label><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></aff><aff id="af23"><label>23</label><institution>Institute of Regional Health Services Research, University of Southern Denmark</institution>,<addr-line>Odense</addr-line>,<country>Denmark</country></aff><aff id="af24"><label>24</label><institution>Odense Patient data Explorative Network (OPEN), Odense University Hospital</institution>,<addr-line>Odense</addr-line>,<country>Denmark</country></aff><aff id="af25"><label>25</label><institution>Institute of Public Health, Environmental Medicine, University of Southern Denmark</institution>,<addr-line>Odense</addr-line>,<country>Denmark</country></aff><author-notes><corresp><label>Correspondence to</label> Dr Abraham Aviv, The Center of Human Development and Aging, New Jersey Medical School, UMDNJ, Newark, NJ 07103; avivab@umdnj.edu Massimo Mangino, King's College London, Department of Twin Research & Genetic Epidemiology, St. Thomas’ Hospital Campus, South Wing, Block D, 3rd Floor, Westminster Bridge Road, London SE1 7EH, UK; <email>massimo.mangino@kcl.ac.uk</email></corresp></author-notes><pub-date pub-type="collection"><year>2015</year></pub-date><pub-date pub-type="epub"><day>26</day><month>1</month><year>2015</year></pub-date><volume>52</volume><issue>3</issue><fpage>157</fpage><lpage>162</lpage><history><date date-type="received"><day>28</day><month>7</month><year>2014</year></date><date date-type="rev-recd"><day>13</day><month>11</month><year>2014</year></date><date date-type="accepted"><day>9</day><month>12</month><year>2014</year></date></history><permissions><copyright-statement>Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions</copyright-statement><copyright-year>2015</copyright-year><license license-type="open-access"><license-p>This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link></license-p></license></permissions><self-uri xlink:title="pdf" xlink:href="jmedgenet-2014-102681.pdf"></self-uri><abstract><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></abstract><kwd-group><kwd>Complex traits</kwd><kwd>Telomere</kwd><kwd>cancer: skin</kwd><kwd>melanoma</kwd></kwd-group><custom-meta-group><custom-meta><meta-name>special-feature</meta-name><meta-value>unlocked</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc><affiliations><list><country><li>Australie</li><li>Danemark</li><li>France</li><li>Israël</li><li>Royaume-Uni</li><li>États-Unis</li></country></list><tree><country name="Royaume-Uni"><noRegion><name sortKey="Mangino, Massimo" sort="Mangino, Massimo" uniqKey="Mangino M" first="Massimo" last="Mangino">Massimo Mangino</name></noRegion><name sortKey="Bataille, Veronique" sort="Bataille, Veronique" uniqKey="Bataille V" first="Veronique" last="Bataille">Veronique Bataille</name><name sortKey="Bataille, Veronique" sort="Bataille, Veronique" uniqKey="Bataille V" first="Veronique" last="Bataille">Veronique Bataille</name><name sortKey="Codd, Veryan" sort="Codd, Veryan" uniqKey="Codd V" first="Veryan" last="Codd">Veryan Codd</name><name sortKey="Codd, Veryan" sort="Codd, Veryan" uniqKey="Codd V" first="Veryan" last="Codd">Veryan Codd</name><name sortKey="Mangino, Massimo" sort="Mangino, Massimo" uniqKey="Mangino M" first="Massimo" last="Mangino">Massimo Mangino</name><name sortKey="Samani, Nilesh J" sort="Samani, Nilesh J" uniqKey="Samani N" first="Nilesh J" last="Samani">Nilesh J. Samani</name><name sortKey="Samani, Nilesh J" sort="Samani, Nilesh J" uniqKey="Samani N" first="Nilesh J" last="Samani">Nilesh J. Samani</name><name sortKey="Spector, Timothy D" sort="Spector, Timothy D" uniqKey="Spector T" first="Timothy D" last="Spector">Timothy D. Spector</name></country><country name="Danemark"><noRegion><name sortKey="Christiansen, Lene" sort="Christiansen, Lene" uniqKey="Christiansen L" first="Lene" last="Christiansen">Lene Christiansen</name></noRegion><name sortKey="Christensen, Kaare" sort="Christensen, Kaare" uniqKey="Christensen K" first="Kaare" last="Christensen">Kaare Christensen</name><name sortKey="Christensen, Kaare" sort="Christensen, Kaare" uniqKey="Christensen K" first="Kaare" last="Christensen">Kaare Christensen</name><name sortKey="Christiansen, Lene" sort="Christiansen, Lene" uniqKey="Christiansen L" first="Lene" last="Christiansen">Lene Christiansen</name><name sortKey="Dalg Rd, Christine" sort="Dalg Rd, Christine" uniqKey="Dalg Rd C" first="Christine" last="Dalg Rd">Christine Dalg Rd</name><name sortKey="Kyvik, Kirsten Ohm" sort="Kyvik, Kirsten Ohm" uniqKey="Kyvik K" first="Kirsten Ohm" last="Kyvik">Kirsten Ohm Kyvik</name><name sortKey="Kyvik, Kirsten Ohm" sort="Kyvik, Kirsten Ohm" uniqKey="Kyvik K" first="Kirsten Ohm" last="Kyvik">Kirsten Ohm Kyvik</name><name sortKey="Kyvik, Kirsten Ohm" sort="Kyvik, Kirsten Ohm" uniqKey="Kyvik K" first="Kirsten Ohm" last="Kyvik">Kirsten Ohm Kyvik</name><name sortKey="Petersen, Inge" sort="Petersen, Inge" uniqKey="Petersen I" first="Inge" last="Petersen">Inge Petersen</name></country><country name="États-Unis"><noRegion><name sortKey="Stone, Rivka" sort="Stone, Rivka" uniqKey="Stone R" first="Rivka" last="Stone">Rivka Stone</name></noRegion><name sortKey="Aviv, Abraham" sort="Aviv, Abraham" uniqKey="Aviv A" first="Abraham" last="Aviv">Abraham Aviv</name><name sortKey="Berenson, Gerald S" sort="Berenson, Gerald S" uniqKey="Berenson G" first="Gerald S" last="Berenson">Gerald S. Berenson</name><name sortKey="Chen, Wei" sort="Chen, Wei" uniqKey="Chen W" first="Wei" last="Chen">Wei Chen</name><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><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><name sortKey="Fitzpatrick, Annette L" sort="Fitzpatrick, Annette L" uniqKey="Fitzpatrick A" first="Annette L" last="Fitzpatrick">Annette L. Fitzpatrick</name><name sortKey="Herbig, Utz" sort="Herbig, Utz" uniqKey="Herbig U" first="Utz" last="Herbig">Utz Herbig</name><name sortKey="Horvath, Kent" sort="Horvath, Kent" uniqKey="Horvath K" first="Kent" last="Horvath">Kent Horvath</name><name sortKey="Hunt, Steven C" sort="Hunt, Steven C" uniqKey="Hunt S" first="Steven C" last="Hunt">Steven C. Hunt</name><name sortKey="Hwang, Shih Jen" sort="Hwang, Shih Jen" uniqKey="Hwang S" first="Shih-Jen" last="Hwang">Shih-Jen Hwang</name><name sortKey="Hwang, Shih Jen" sort="Hwang, Shih Jen" uniqKey="Hwang S" first="Shih-Jen" last="Hwang">Shih-Jen Hwang</name><name sortKey="Kimura, Masayuki" sort="Kimura, Masayuki" uniqKey="Kimura M" first="Masayuki" last="Kimura">Masayuki Kimura</name><name sortKey="Levy, Daniel" sort="Levy, Daniel" uniqKey="Levy D" first="Daniel" last="Levy">Daniel Levy</name><name sortKey="Levy, Daniel" sort="Levy, Daniel" uniqKey="Levy D" first="Daniel" last="Levy">Daniel Levy</name><name sortKey="Reiner, Alex P" sort="Reiner, Alex P" uniqKey="Reiner A" first="Alex P" last="Reiner">Alex P. Reiner</name><name sortKey="Reiner, Alex P" sort="Reiner, Alex P" uniqKey="Reiner A" first="Alex P" last="Reiner">Alex P. Reiner</name><name sortKey="Schork, Nicholas J" sort="Schork, Nicholas J" uniqKey="Schork N" first="Nicholas J" last="Schork">Nicholas J. Schork</name><name sortKey="Tishkoff, Sarah" sort="Tishkoff, Sarah" uniqKey="Tishkoff S" first="Sarah" last="Tishkoff">Sarah Tishkoff</name></country><country name="Israël"><noRegion><name sortKey="Kark, Jeremy D" sort="Kark, Jeremy D" uniqKey="Kark J" first="Jeremy D" last="Kark">Jeremy D. Kark</name></noRegion><name sortKey="Nassar, Hisham" sort="Nassar, Hisham" uniqKey="Nassar H" first="Hisham" last="Nassar">Hisham Nassar</name><name sortKey="Sinnreich, Ronit" sort="Sinnreich, Ronit" uniqKey="Sinnreich R" first="Ronit" last="Sinnreich">Ronit Sinnreich</name></country><country name="France"><noRegion><name sortKey="Benetos, Athanase" sort="Benetos, Athanase" uniqKey="Benetos A" first="Athanase" last="Benetos">Athanase Benetos</name></noRegion></country><country name="Australie"><noRegion><name sortKey="Nyholt, Dale R" sort="Nyholt, Dale R" uniqKey="Nyholt D" first="Dale R" last="Nyholt">Dale R. 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