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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.

SUBMITTER: Codd V 

PROVIDER: S-EPMC4006270 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Identification of seven loci affecting mean telomere length and their association with disease.

Codd Veryan V   Nelson Christopher P CP   Albrecht Eva E   Mangino Massimo M   Deelen Joris J   Buxton Jessica L JL   Hottenga Jouke Jan JJ   Fischer Krista K   Esko Tõnu T   Surakka Ida I   Broer Linda L   Nyholt Dale R DR   Mateo Leach Irene I   Salo Perttu P   Hägg Sara S   Matthews Mary K MK   Palmen Jutta J   Norata Giuseppe D GD   O'Reilly Paul F PF   Saleheen Danish D   Amin Najaf N   Balmforth Anthony J AJ   Beekman Marian M   de Boer Rudolf A RA   Böhringer Stefan S   Braund Peter S PS   Burton Paul R PR   de Craen Anton J M AJ   Denniff Matthew M   Dong Yanbin Y   Douroudis Konstantinos K   Dubinina Elena E   Eriksson Johan G JG   Garlaschelli Katia K   Guo Dehuang D   Hartikainen Anna-Liisa AL   Henders Anjali K AK   Houwing-Duistermaat Jeanine J JJ   Kananen Laura L   Karssen Lennart C LC   Kettunen Johannes J   Klopp Norman N   Lagou Vasiliki V   van Leeuwen Elisabeth M EM   Madden Pamela A PA   Mägi Reedik R   Magnusson Patrik K E PK   Männistö Satu S   McCarthy Mark I MI   Medland Sarah E SE   Mihailov Evelin E   Montgomery Grant W GW   Oostra Ben A BA   Palotie Aarno A   Peters Annette A   Pollard Helen H   Pouta Anneli A   Prokopenko Inga I   Ripatti Samuli S   Salomaa Veikko V   Suchiman H Eka D HE   Valdes Ana M AM   Verweij Niek N   Viñuela Ana A   Wang Xiaoling X   Wichmann H-Erich HE   Widen Elisabeth E   Willemsen Gonneke G   Wright Margaret J MJ   Xia Kai K   Xiao Xiangjun X   van Veldhuisen Dirk J DJ   Catapano Alberico L AL   Tobin Martin D MD   Hall Alistair S AS   Blakemore Alexandra I F AI   van Gilst Wiek H WH   Zhu Haidong H   Erdmann Jeanette J   Reilly Muredach P MP   Kathiresan Sekar S   Schunkert Heribert H   Talmud Philippa J PJ   Pedersen Nancy L NL   Perola Markus M   Ouwehand Willem W   Kaprio Jaakko J   Martin Nicholas G NG   van Duijn Cornelia M CM   Hovatta Iiris I   Gieger Christian C   Metspalu Andres A   Boomsma Dorret I DI   Jarvelin Marjo-Riitta MR   Slagboom P Eline PE   Thompson John R JR   Spector Tim D TD   van der Harst Pim P   Samani Nilesh J NJ  

Nature genetics 20130401 4

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  ...[more]

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