Open Access
Identification of seven loci affecting mean telomere length and their association with disease
Veryan Codd,Christopher P. Nelson,Eva Albrecht,Massimo Mangino,Joris Deelen,Jessica L. Buxton,Jouke-Jan Hottenga,Krista Fischer,Tõnu Esko,Ida Surakka,Linda Broer,Dale R. Nyholt,Irene Mateo Leach,Perttu Salo,Sara Hägg,Mary K. Matthews,Jutta Palmen,Giuseppe Danilo Norata,Paul F. O'Reilly,Danish Saleheen,Najaf Amin,Anthony J. Balmforth,Marian Beekman,Rudolf A. de Boer,Stefan Böhringer,Peter S. Braund,Paul Burton,Anton J. M. de Craen,Matthew Denniff,Yanbin Dong,Konstantinos Douroudis,Elena Dubinina,Johan G. Eriksson,Katia Garlaschelli,Dehuang Guo,Anna-Liisa Hartikainen,Anjali K. Henders,Jeanine J. Houwing-Duistermaat,Laura Kananen,Lennart C. Karssen,Johannes Kettunen,Norman Klopp,Vasiliki Lagou,Elisabeth M. van Leeuwen,Pamela A. F. Madden,Reedik Maegi,Patrik K. E. Magnusson,Satu Männistö,Mark I. McCarthy,Sarah E. Medland,Evelin Mihailov,Grant W. Montgomery,Ben A. Oostra,Aarno Palotie,Annette Peters,Helen Pollard,Anneli Pouta,Inga Prokopenko,Samuli Ripatti,Veikko Salomaa,H. Eka D. Suchiman,Ana M. Valdes,Niek Verweij,Ana Viñuela,Xiaoling Wang,H-Erich Wichmann,Elisabeth Widen,Gonneke Willemsen,Margaret J. Wright,Kai Xia,Xiangjun Xiao,Dirk J. van Veldhuisen,Alberico L. Catapano,Martin D. Tobin,Alistair S. Hall,Alexandra I. F. Blakemore,Wiek H. van Gilst,Haidong Zhu,Jeanette Erdmann,Muredach P. Reilly,Sekar Kathiresan,Heribert Schunkert,Philippa J. Talmud,Nancy L. Pedersen,Markus Perola,Willem H. Ouwehand,Jaakko Kaprio,Nicholas G. Martin,Cornelia M. van Duijn,Iris Hovatta,Christian Gieger,Andres Metspalu,Dorret I. Boomsma,Marjo-Riitta Järvelin,P. Eline Slagboom,John R Thompson,Tim D. Spector,Pim van der Harst,Nilesh J. Samani +98 more
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TLDR
In this article, a genome-wide meta-analysis of 37,684 individuals with replication of selected variants in an additional 10,739 individuals was carried out to identify seven loci, including five new loci associated with mean leukocyte telomere length (LTL).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.read more
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Human telomere biology: A contributory and interactive factor in aging, disease risks, and protection
TL;DR: These and other recent findings highlight both causal and potentiating roles for telomere attrition in human diseases, especially in diseases of human aging and in some aging-related processes.
Journal ArticleDOI
Leucocyte telomere length and risk of cardiovascular disease: systematic review and meta-analysis.
Philip C Haycock,Emma E Heydon,Stephen Kaptoge,Adam S. Butterworth,Alexander M. W. Cargill Thompson,Peter Willeit +5 more
TL;DR: In this article, the authors assess the association between leucocyte telomere length and risk of cardiovascular disease using a systematic review and meta-analysis, and show that there is an inverse association between the shortest and longest third of leucomeres length and the risk of coronary heart disease.
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Red blood cell distribution width: A simple parameter with multiple clinical applications
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Biological Age Predictors
TL;DR: Current state-of-the-art findings considering six potential types of biological age predictors are summarized, including epigenetic clocks, telomere length, transcriptomic predictors, proteomic Predictors, metabolomics-based predictor, and composite biomarker predictors.
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More than a feeling: A unified view of stress measurement for population science.
Elissa S. Epel,Alexandra D. Crosswell,Stefanie E. Mayer,Aric A. Prather,George M. Slavich,Eli Puterman,Wendy Berry Mendes +6 more
TL;DR: An integrative working model is articulated, highlighting how stressor exposures across the life course influence habitual responding and stress reactivity, and how health behaviors interact with stress, and a Stress Typology articulating timescales for stress measurement is offered.
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TL;DR: This study has demonstrated that careful use of a shared control group represents a safe and effective approach to GWA analyses of multiple disease phenotypes; generated a genome-wide genotype database for future studies of common diseases in the British population; and shown that, provided individuals with non-European ancestry are excluded, the extent of population stratification in theBritish population is generally modest.
Journal ArticleDOI
Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm.
TL;DR: This protocol describes the use of the 'Sorting Tolerant From Intolerant' (SIFT) algorithm in predicting whether an AAS affects protein function.
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