Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
25624462
TITLE
DCAF4, a novel gene associated with leucocyte telomere length.
ABSTRACT
BACKGROUND NlmCategory: BACKGROUND
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 DCAF4 (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).
RESULTS NlmCategory: RESULTS
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 DCAF4. Notably, eQTL analysis showed that rs2535913 is associated with decline in DCAF4 expressions in both lymphoblastoid cells and sun-exposed skin (p=4.1×10(-3) and 2×10(-3), 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(-169) to 3.42×10(-24).
CONCLUSIONS NlmCategory: CONCLUSIONS
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.
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.
DATE PUBLISHED
2015 Mar
HISTORY
PUBSTATUS PUBSTATUSDATE
aheadofprint 2015/01/26
entrez 2015/01/28 06:00
pubmed 2015/01/28 06:00
medline 2016/03/02 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Mangino M Mangino Massimo M Department of Twin Research and Genetic Epidemiology, King's College London, London, UK National Institute for Health Research (NIHR) Biomedical Research Centre at Guy's and St. Thomas' Foundation Trust, London, UK.
Christiansen L Christiansen Lene L Epidemiology Unit, The Danish Aging Research Center and The Danish Twin Registry, Institute of Public Health, University of Southern Denmark, Odense, Denmark Department of Clinical Genetics, and Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark.
Stone R Stone Rivka R Center of Human Development and Aging, Rutgers, The State University of New Jersey, New Jersey Medical School, Newark, New Jersey, USA.
Hunt SC Hunt Steven C SC Cardiovascular Genetics Division, Department of Medicine, University of Utah, Salt Lake City, Utah, USA.
Horvath K Horvath Kent K Center of Human Development and Aging, Rutgers, The State University of New Jersey, New Jersey Medical School, Newark, New Jersey, USA.
Eisenberg DT Eisenberg Dan T A DT Department of Anthropology, University of Washington, Seattle, Washington, USA Center for Studies in Demography and Ecology, University of Washington, Seattle, Washington, USA.
Kimura M Kimura Masayuki M Center of Human Development and Aging, Rutgers, The State University of New Jersey, New Jersey Medical School, Newark, New Jersey, USA.
Petersen I Petersen Inge I Epidemiology Unit, The Danish Aging Research Center and The Danish Twin Registry, Institute of Public Health, University of Southern Denmark, Odense, Denmark.
Kark JD Kark Jeremy D JD Epidemiology Unit, Hebrew University-Hadassah School of Public Health and Community Medicine, Jerusalem, Israel.
Herbig U Herbig Utz U Center of Human Development and Aging, Rutgers, The State University of New Jersey, New Jersey Medical School, Newark, New Jersey, USA.
Reiner AP Reiner Alex P AP Department of Epidemiology, University of Washington, Seattle, Washington, USA Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Benetos A Benetos Athanase A Department of Geriatrics, Universite de Lorraine INSERM U961, Nancy, France.
Codd V Codd Veryan V Department of Cardiovascular Sciences, University of Leicester, Leicester, UK National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK.
Nyholt DR Nyholt Dale R DR QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Sinnreich R Sinnreich Ronit R Epidemiology Unit, Hebrew University-Hadassah School of Public Health and Community Medicine, Jerusalem, Israel.
Christensen K Christensen Kaare K Epidemiology Unit, The Danish Aging Research Center and The Danish Twin Registry, Institute of Public Health, University of Southern Denmark, Odense, Denmark Department of Clinical Genetics, and Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark.
Nassar H Nassar Hisham H Department of Cardiology, Hadassah University Medical Center, Jerusalem, Israel.
Hwang SJ Hwang Shih-Jen SJ Population Sciences Branch of the National Heart, Lung and Blood Institute, Bethesda, Maryland, USA The Framingham Heart Study, Framingham, Massachusetts, USA.
Levy D Levy Daniel D Population Sciences Branch of the National Heart, Lung and Blood Institute, Bethesda, Maryland, USA The Framingham Heart Study, Framingham, Massachusetts, USA.
Bataille V Bataille Veronique V Department of Twin Research and Genetic Epidemiology, King's College London, London, UK Department of Dermatology, West Herts NHS Trust, Herts, UK.
Fitzpatrick AL Fitzpatrick Annette L AL Department of Epidemiology, University of Washington, Seattle, Washington, USA.
Chen W Chen Wei W Center for Cardiovascular Health, Tulane University, New Orleans, Louisiana, USA.
Berenson GS Berenson Gerald S GS Center for Cardiovascular Health, Tulane University, New Orleans, Louisiana, USA.
Samani NJ Samani Nilesh J NJ Department of Cardiovascular Sciences, University of Leicester, Leicester, UK National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK.
Martin NG Martin Nicholas G NG QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Tishkoff S Tishkoff Sarah S Department of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Schork NJ Schork Nicholas J NJ Department of Molecular and Experimental Medicine, The Scripps Research Institute, San Diego, California, USA.
Kyvik KO Kyvik Kirsten Ohm KO Epidemiology Unit, The Danish Aging Research Center and The Danish Twin Registry, Institute of Public Health, University of Southern Denmark, Odense, Denmark Institute of Regional Health Services Research, University of Southern Denmark, Odense, Denmark Odense Patient data Explorative Network (OPEN), Odense University Hospital, Odense, Denmark.
Dalgård C Dalgård Christine C Institute of Public Health, Environmental Medicine, University of Southern Denmark, Odense, Denmark.
Spector TD Spector Timothy D TD Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
Aviv A Aviv Abraham A Center of Human Development and Aging, Rutgers, The State University of New Jersey, New Jersey Medical School, Newark, New Jersey, USA.
INVESTIGATORS
JOURNAL
VOLUME: 52
ISSUE: 3
TITLE: Journal of medical genetics
ISOABBREVIATION: J. Med. Genet.
YEAR: 2015
MONTH: Mar
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1468-6244
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: J Med Genet
COUNTRY: England
ISSNLINKING: 0022-2593
NLMUNIQUEID: 2985087R
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
Cites Am J Epidemiol. 2013 Apr 1;177(7):617-24 23444102
Cites J Natl Cancer Inst. 2013 Apr 3;105(7):448-9 23468461
Cites Genes Chromosomes Cancer. 2013 Jul;52(7):595-609 23629941
Cites Nat Genet. 2013 Jun;45(6):580-5 23715323
Cites Cancer Epidemiol. 2013 Aug;37(4):434-9 23523330
Cites Atherosclerosis. 2013 Aug;229(2):363-8 23880188
Cites Eur J Hum Genet. 2013 Oct;21(10):1163-8 23321625
Cites Int J Cancer. 2013 Dec 1;133(11):2672-80 23674344
Cites Nat Genet. 2014 May;46(5):482-6 24686846
Cites Nat Genet. 2014 May;46(5):478-81 24686849
Cites Cancer Res. 2014 May 1;74(9):2476-86 24618342
Cites Cancer Res. 2014 Aug 1;74(15):4090-8 24853549
Cites J Natl Cancer Inst. 2014 Oct;106(10). pii: dju267. doi: 10.1093/jnci/dju267 25231748
Cites J Aging Health. 2001 Feb;13(1):32-46 11503846
Cites J Am Geriatr Soc. 2001 Jul;49(7):900-8 11527481
Cites Nat Genet. 2002 Jan;30(1):97-101 11731797
Cites Circulation. 2002 Mar 12;105(10):1202-7 11889014
Cites Twin Res. 2002 Oct;5(5):352-7 12537858
Cites Eur J Cancer. 2003 Jul;39(10):1341-7 12826035
Cites BMJ. 2003 Sep 6;327(7414):557-60 12958120
Cites Oncogene. 1994 Feb;9(2):405-15 8290253
Cites Mol Cell Biol. 1998 Jan;18(1):240-9 9418871
Cites J Natl Cancer Inst. 2005 Nov 2;97(21):1589-600 16264179
Cites Cell Cycle. 2006 May;5(9):930-5 16628012
Cites Cell. 2007 Mar 9;128(5):853-64 17350573
Cites Diabetologia. 2007 Sep;50(9):1880-8 17624514
Cites J Invest Dermatol. 2009 Sep;129(9):2211-9 19357710
Cites PLoS One. 2009;4(12):e8021 19956599
Cites Cancer Epidemiol Biomarkers Prev. 2010 Jan;19(1):65-73 20056624
Cites Cancer Epidemiol Biomarkers Prev. 2010 Jan;19(1):111-20 20056629
Cites Proc Natl Acad Sci U S A. 2010 May 18;107(20):9293-8 20421499
Cites BMC Bioinformatics. 2010;11:288 20509871
Cites Bioinformatics. 2010 Sep 1;26(17):2190-1 20616382
Cites Nat Protoc. 2010 Sep;5(9):1596-607 21085125
Cites FEBS Lett. 2011 Sep 16;585(18):2818-25 21550341
Cites Genome Biol. 2011;12(4):220 21554755
Cites J Am Acad Dermatol. 2011 Nov;65(5 Suppl 1):S50-7 22018067
Cites Nucleic Acids Res. 2011 Nov 1;39(20):e134 21824912
Cites Cancer Res. 2011 Nov 1;71(21):6758-63 22028319
Cites Int J Biochem Cell Biol. 2011 Dec;43(12):1664-7 21959250
Cites Nucleic Acids Res. 2012 Jan;40(Database issue):D930-4 22064851
Cites Mutat Res. 2012 Feb 1;730(1-2):68-74 21600224
Cites Mutat Res. 2012 Feb 1;730(1-2):75-84 21756922
Cites Am J Clin Nutr. 2012 Feb;95(2):479-87 22237065
Cites Aging Cell. 2012 Apr;11(2):223-7 22136229
Cites J Invest Dermatol. 2012 Jul;132(7):1763-74 22475760
Cites Nat Genet. 2012 Oct;44(10):1084-9 22941192
Cites EMBO J. 2012 Nov 5;31(21):4165-78 23010778
Cites Hum Mol Genet. 2012 Dec 15;21(24):5385-94 23001564
Cites Science. 2013 Feb 22;339(6122):959-61 23348503
Cites Science. 2013 Feb 22;339(6122):957-9 23348506
Cites Nat Commun. 2013;4:1597 23511462
Cites Nat Genet. 2013 Apr;45(4):422-7, 427e1-2 23535734
GRANTS
GRANTID AGENCY COUNTRY
2R01AG016592 NIA NIH HHS United States
5R01ES021724 NIEHS NIH HHS United States
AG023629 NIA NIH HHS United States
HHSN268200800007C PHS HHS United States
HHSN268201200036C PHS HHS United States
HL055673 NHLBI NIH HHS United States
HL080295 NHLBI NIH HHS United States
HL087652 NHLBI NIH HHS United States
HL105756 NHLBI NIH HHS United States
HL54471 NHLBI NIH HHS United States
HL54472 NHLBI NIH HHS United States
HL54473 NHLBI NIH HHS United States
HL54495 NHLBI NIH HHS United States
HL54496 NHLBI NIH HHS United States
HL54509 NHLBI NIH HHS United States
HL54515 NHLBI NIH HHS United States
N01-HC-25195 NHLBI NIH HHS United States
N01HC55222 NHLBI NIH HHS United States
N01HC85079 NHLBI NIH HHS United States
N01HC85080 NHLBI NIH HHS United States
N01HC85081 NHLBI NIH HHS United States
N01HC85082 NHLBI NIH HHS United States
N01HC85083 NHLBI NIH HHS United States
N01HC85086 NHLBI NIH HHS United States
R01 AG016592 NIA NIH HHS United States
R01 HL116446 NHLBI NIH HHS United States
R01AG030678 NIA NIH HHS United States
R01AG20132 NIA NIH HHS United States
R01AG21593 NIA NIH HHS United States
R24 HD042828 NICHD NIH HHS United States
British Heart Foundation United Kingdom
Intramural NIH HHS United States
Wellcome Trust United Kingdom
GENERAL NOTE
KEYWORDS
KEYWORD
Complex traits
Telomere
cancer: skin
melanoma
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Alleles
Carrier Proteins genetics
Gene Expression Regulation genetics
Genome-Wide Association Study genetics
Humans genetics
Leukocytes cytology
Melanoma pathology
Risk Factors pathology
Telomere genetics
Telomere Homeostasis genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Carrier Proteins
0 WDR21A protein, human
OTHER ID's
OTHERID SOURCE
PMC4345921 NLM