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Loci for human leukocyte telomere length in the Singaporean Chinese population and trans-ethnic genetic studies

Genetic factors underlying leukocyte telomere length (LTL) may provide insights into telomere homeostasis, with direct links to disease susceptibility. Genetic evaluation of 23,096 Singaporean Chinese samples identifies 10 genome-wide loci (P < 5 × 10(−8)). Several of these contain candidate gene...

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Autores principales: Dorajoo, Rajkumar, Chang, Xuling, Gurung, Resham Lal, Li, Zheng, Wang, Ling, Wang, Renwei, Beckman, Kenneth B., Adams-Haduch, Jennifer, M, Yiamunaa, Liu, Sylvia, Meah, Wee Yang, Sim, Kar Seng, Lim, Su Chi, Friedlander, Yechiel, Liu, Jianjun, van Dam, Rob M., Yuan, Jian-Min, Koh, Woon-Puay, Khor, Chiea Chuen, Heng, Chew-Kiat
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6554354/
https://www.ncbi.nlm.nih.gov/pubmed/31171785
http://dx.doi.org/10.1038/s41467-019-10443-2
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author Dorajoo, Rajkumar
Chang, Xuling
Gurung, Resham Lal
Li, Zheng
Wang, Ling
Wang, Renwei
Beckman, Kenneth B.
Adams-Haduch, Jennifer
M, Yiamunaa
Liu, Sylvia
Meah, Wee Yang
Sim, Kar Seng
Lim, Su Chi
Friedlander, Yechiel
Liu, Jianjun
van Dam, Rob M.
Yuan, Jian-Min
Koh, Woon-Puay
Khor, Chiea Chuen
Heng, Chew-Kiat
author_facet Dorajoo, Rajkumar
Chang, Xuling
Gurung, Resham Lal
Li, Zheng
Wang, Ling
Wang, Renwei
Beckman, Kenneth B.
Adams-Haduch, Jennifer
M, Yiamunaa
Liu, Sylvia
Meah, Wee Yang
Sim, Kar Seng
Lim, Su Chi
Friedlander, Yechiel
Liu, Jianjun
van Dam, Rob M.
Yuan, Jian-Min
Koh, Woon-Puay
Khor, Chiea Chuen
Heng, Chew-Kiat
author_sort Dorajoo, Rajkumar
collection PubMed
description Genetic factors underlying leukocyte telomere length (LTL) may provide insights into telomere homeostasis, with direct links to disease susceptibility. Genetic evaluation of 23,096 Singaporean Chinese samples identifies 10 genome-wide loci (P < 5 × 10(−8)). Several of these contain candidate genes (TINF2, PARP1, TERF1, ATM and POT1) with potential roles in telomere biology and DNA repair mechanisms. Meta-analyses with additional 37,505 European individuals reveals six more genome-wide loci, including associations at MPHOSPH6, NKX2-3 and TYMS. We demonstrate that longer LTL associates with protection against respiratory disease mortality [HR = 0.854(0.804–0.906), P = 1.88 × 10(−7)] in the Singaporean Chinese samples. We further show that the LTL reducing SNP rs7253490 associates with respiratory infections (P = 7.44 × 10(−4)) although this effect may not be strongly mediated through LTL. Our data expands on the genetic basis of LTL and may indicate on a potential role of LTL in immune competence.
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spelling pubmed-65543542019-06-17 Loci for human leukocyte telomere length in the Singaporean Chinese population and trans-ethnic genetic studies Dorajoo, Rajkumar Chang, Xuling Gurung, Resham Lal Li, Zheng Wang, Ling Wang, Renwei Beckman, Kenneth B. Adams-Haduch, Jennifer M, Yiamunaa Liu, Sylvia Meah, Wee Yang Sim, Kar Seng Lim, Su Chi Friedlander, Yechiel Liu, Jianjun van Dam, Rob M. Yuan, Jian-Min Koh, Woon-Puay Khor, Chiea Chuen Heng, Chew-Kiat Nat Commun Article Genetic factors underlying leukocyte telomere length (LTL) may provide insights into telomere homeostasis, with direct links to disease susceptibility. Genetic evaluation of 23,096 Singaporean Chinese samples identifies 10 genome-wide loci (P < 5 × 10(−8)). Several of these contain candidate genes (TINF2, PARP1, TERF1, ATM and POT1) with potential roles in telomere biology and DNA repair mechanisms. Meta-analyses with additional 37,505 European individuals reveals six more genome-wide loci, including associations at MPHOSPH6, NKX2-3 and TYMS. We demonstrate that longer LTL associates with protection against respiratory disease mortality [HR = 0.854(0.804–0.906), P = 1.88 × 10(−7)] in the Singaporean Chinese samples. We further show that the LTL reducing SNP rs7253490 associates with respiratory infections (P = 7.44 × 10(−4)) although this effect may not be strongly mediated through LTL. Our data expands on the genetic basis of LTL and may indicate on a potential role of LTL in immune competence. Nature Publishing Group UK 2019-06-06 /pmc/articles/PMC6554354/ /pubmed/31171785 http://dx.doi.org/10.1038/s41467-019-10443-2 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Dorajoo, Rajkumar
Chang, Xuling
Gurung, Resham Lal
Li, Zheng
Wang, Ling
Wang, Renwei
Beckman, Kenneth B.
Adams-Haduch, Jennifer
M, Yiamunaa
Liu, Sylvia
Meah, Wee Yang
Sim, Kar Seng
Lim, Su Chi
Friedlander, Yechiel
Liu, Jianjun
van Dam, Rob M.
Yuan, Jian-Min
Koh, Woon-Puay
Khor, Chiea Chuen
Heng, Chew-Kiat
Loci for human leukocyte telomere length in the Singaporean Chinese population and trans-ethnic genetic studies
title Loci for human leukocyte telomere length in the Singaporean Chinese population and trans-ethnic genetic studies
title_full Loci for human leukocyte telomere length in the Singaporean Chinese population and trans-ethnic genetic studies
title_fullStr Loci for human leukocyte telomere length in the Singaporean Chinese population and trans-ethnic genetic studies
title_full_unstemmed Loci for human leukocyte telomere length in the Singaporean Chinese population and trans-ethnic genetic studies
title_short Loci for human leukocyte telomere length in the Singaporean Chinese population and trans-ethnic genetic studies
title_sort loci for human leukocyte telomere length in the singaporean chinese population and trans-ethnic genetic studies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6554354/
https://www.ncbi.nlm.nih.gov/pubmed/31171785
http://dx.doi.org/10.1038/s41467-019-10443-2
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