Genetic Epidemiology, Translational Neurogenomics, Psychiatric 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
23535734
TITLE
Identification of seven loci affecting mean telomere length and their association with disease.
ABSTRACT
Interindividual variation in mean leukocyte telomere length (LTL) is associated with cancer and several age-associated diseases. We report here a genome-wide meta-analysis of 37,684 individuals with replication of selected variants in an additional 10,739 individuals. We identified seven loci, including five new loci, associated with mean LTL (P < 5 × 10(-8)). Five of the loci contain candidate genes (TERC, TERT, NAF1, OBFC1 and RTEL1) that are known to be involved in telomere biology. Lead SNPs at two loci (TERC and TERT) associate with several cancers and other diseases, including idiopathic pulmonary fibrosis. Moreover, a genetic risk score analysis combining lead variants at all 7 loci in 22,233 coronary artery disease cases and 64,762 controls showed an association of the alleles associated with shorter LTL with increased risk of coronary artery disease (21% (95% confidence interval, 5-35%) per standard deviation in LTL, P = 0.014). Our findings support a causal role of telomere-length variation in some age-related diseases.
DATE PUBLISHED
2013 Apr
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2012/06/26
accepted 2012/12/19
entrez 2013/03/29 06:00
pubmed 2013/03/29 06:00
medline 2013/05/23 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Codd V Codd Veryan V Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.
Nelson CP Nelson Christopher P CP
Albrecht E Albrecht Eva E
Mangino M Mangino Massimo M
Deelen J Deelen Joris J
Buxton JL Buxton Jessica L JL
Hottenga JJ Hottenga Jouke Jan JJ
Fischer K Fischer Krista K
Esko T Esko Tõnu T
Surakka I Surakka Ida I
Broer L Broer Linda L
Nyholt DR Nyholt Dale R DR
Mateo Leach I Mateo Leach Irene I
Salo P Salo Perttu P
Hägg S Hägg Sara S
Matthews MK Matthews Mary K MK
Palmen J Palmen Jutta J
Norata GD Norata Giuseppe D GD
O'Reilly PF O'Reilly Paul F PF
Saleheen D Saleheen Danish D
Amin N Amin Najaf N
Balmforth AJ Balmforth Anthony J AJ
Beekman M Beekman Marian M
de Boer RA de Boer Rudolf A RA
Böhringer S Böhringer Stefan S
Braund PS Braund Peter S PS
Burton PR Burton Paul R PR
de Craen AJ de Craen Anton J M AJ
Denniff M Denniff Matthew M
Dong Y Dong Yanbin Y
Douroudis K Douroudis Konstantinos K
Dubinina E Dubinina Elena E
Eriksson JG Eriksson Johan G JG
Garlaschelli K Garlaschelli Katia K
Guo D Guo Dehuang D
Hartikainen AL Hartikainen Anna-Liisa AL
Henders AK Henders Anjali K AK
Houwing-Duistermaat JJ Houwing-Duistermaat Jeanine J JJ
Kananen L Kananen Laura L
Karssen LC Karssen Lennart C LC
Kettunen J Kettunen Johannes J
Klopp N Klopp Norman N
Lagou V Lagou Vasiliki V
van Leeuwen EM van Leeuwen Elisabeth M EM
Madden PA Madden Pamela A PA
Mägi R Mägi Reedik R
Magnusson PK Magnusson Patrik K E PK
Männistö S Männistö Satu S
McCarthy MI McCarthy Mark I MI
Medland SE Medland Sarah E SE
Mihailov E Mihailov Evelin E
Montgomery GW Montgomery Grant W GW
Oostra BA Oostra Ben A BA
Palotie A Palotie Aarno A
Peters A Peters Annette A
Pollard H Pollard Helen H
Pouta A Pouta Anneli A
Prokopenko I Prokopenko Inga I
Ripatti S Ripatti Samuli S
Salomaa V Salomaa Veikko V
Suchiman HE Suchiman H Eka D HE
Valdes AM Valdes Ana M AM
Verweij N Verweij Niek N
Viñuela A Viñuela Ana A
Wang X Wang Xiaoling X
Wichmann HE Wichmann H-Erich HE
Widen E Widen Elisabeth E
Willemsen G Willemsen Gonneke G
Wright MJ Wright Margaret J MJ
Xia K Xia Kai K
Xiao X Xiao Xiangjun X
van Veldhuisen DJ van Veldhuisen Dirk J DJ
Catapano AL Catapano Alberico L AL
Tobin MD Tobin Martin D MD
Hall AS Hall Alistair S AS
Blakemore AI Blakemore Alexandra I F AI
van Gilst WH van Gilst Wiek H WH
Zhu H Zhu Haidong H
CARDIoGRAM consortium
Erdmann J Erdmann Jeanette J
Reilly MP Reilly Muredach P MP
Kathiresan S Kathiresan Sekar S
Schunkert H Schunkert Heribert H
Talmud PJ Talmud Philippa J PJ
Pedersen NL Pedersen Nancy L NL
Perola M Perola Markus M
Ouwehand W Ouwehand Willem W
Kaprio J Kaprio Jaakko J
Martin NG Martin Nicholas G NG
van Duijn CM van Duijn Cornelia M CM
Hovatta I Hovatta Iiris I
Gieger C Gieger Christian C
Metspalu A Metspalu Andres A
Boomsma DI Boomsma Dorret I DI
Jarvelin MR Jarvelin Marjo-Riitta MR
Slagboom PE Slagboom P Eline PE
Thompson JR Thompson John R JR
Spector TD Spector Tim D TD
van der Harst P van der Harst Pim P
Samani NJ Samani Nilesh J NJ
INVESTIGATORS
JOURNAL
VOLUME: 45
ISSUE: 4
TITLE: Nature genetics
ISOABBREVIATION: Nat Genet
YEAR: 2013
MONTH: Apr
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1546-1718
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Nat Genet
COUNTRY: United States
ISSNLINKING: 1061-4036
NLMUNIQUEID: 9216904
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
090532 Wellcome Trust United Kingdom
G0902313 Medical Research Council United Kingdom
MR/K014536/1 Medical Research Council United Kingdom
R56 DA012854 NIDA NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Biomarkers, Tumor genetics
Case-Control Studies genetics
Disease genetics
Female genetics
Genetic Loci genetics
Genetic Predisposition to Disease genetics
Genome-Wide Association Study genetics
Humans genetics
Leukocytes metabolism
Male metabolism
Meta-Analysis as Topic metabolism
Risk Factors metabolism
Telomerase genetics
Telomere genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Biomarkers, Tumor
EC 2.7.7.49 TERT protein, human
EC 2.7.7.49 Telomerase
OTHER ID's
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