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Low frequency variants associated with leukocyte telomere length in the Singapore Chinese population
The role of low frequency variants associated with telomere length homeostasis in chronic diseases and mortalities is relatively understudied in the East-Asian population. Here we evaluated low frequency variants, including 1,915,154 Asian specific variants, for leukocyte telomere length (LTL) assoc...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093266/ https://www.ncbi.nlm.nih.gov/pubmed/33941849 http://dx.doi.org/10.1038/s42003-021-02056-7 |
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author | Chang, Xuling Gurung, Resham L. Wang, Ling Jin, Aizhen Li, Zheng Wang, Renwei Beckman, Kenneth B. Adams-Haduch, Jennifer Meah, Wee Yang Sim, Kar Seng Lim, Weng Khong Davila, Sonia Tan, Patrick Teo, Jing Xian Yeo, Khung Keong M., Yiamunaa Liu, Sylvia Lim, Su Chi Liu, Jianjun van Dam, Rob M. Friedlander, Yechiel Koh, Woon-Puay Yuan, Jian-Min Khor, Chiea Chuen Heng, Chew-Kiat Dorajoo, Rajkumar |
author_facet | Chang, Xuling Gurung, Resham L. Wang, Ling Jin, Aizhen Li, Zheng Wang, Renwei Beckman, Kenneth B. Adams-Haduch, Jennifer Meah, Wee Yang Sim, Kar Seng Lim, Weng Khong Davila, Sonia Tan, Patrick Teo, Jing Xian Yeo, Khung Keong M., Yiamunaa Liu, Sylvia Lim, Su Chi Liu, Jianjun van Dam, Rob M. Friedlander, Yechiel Koh, Woon-Puay Yuan, Jian-Min Khor, Chiea Chuen Heng, Chew-Kiat Dorajoo, Rajkumar |
author_sort | Chang, Xuling |
collection | PubMed |
description | The role of low frequency variants associated with telomere length homeostasis in chronic diseases and mortalities is relatively understudied in the East-Asian population. Here we evaluated low frequency variants, including 1,915,154 Asian specific variants, for leukocyte telomere length (LTL) associations among 25,533 Singapore Chinese samples. Three East Asian specific variants in/near POT1, TERF1 and STN1 genes are associated with LTL (Meta-analysis P 2.49×10(−14)–6.94×10(−10)). Rs79314063, a missense variant (p.Asp410His) at POT1, shows effect 5.3 fold higher and independent of a previous common index SNP. TERF1 (rs79617270) and STN1 (rs139620151) are linked to LTL-associated common index SNPs at these loci. Rs79617270 is associated with cancer mortality [HR(95%CI) = 1.544 (1.173, 2.032), P(Adj) = 0.018] and 4.76% of the association between the rs79617270 and colon cancer is mediated through LTL. Overall, genetically determined LTL is particularly associated with lung adenocarcinoma [HR(95%CI) = 1.123 (1.051, 1.201), P(adj) = 0.007]. Ethnicity-specific low frequency variants may affect LTL homeostasis and associate with certain cancers. |
format | Online Article Text |
id | pubmed-8093266 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-80932662021-05-05 Low frequency variants associated with leukocyte telomere length in the Singapore Chinese population Chang, Xuling Gurung, Resham L. Wang, Ling Jin, Aizhen Li, Zheng Wang, Renwei Beckman, Kenneth B. Adams-Haduch, Jennifer Meah, Wee Yang Sim, Kar Seng Lim, Weng Khong Davila, Sonia Tan, Patrick Teo, Jing Xian Yeo, Khung Keong M., Yiamunaa Liu, Sylvia Lim, Su Chi Liu, Jianjun van Dam, Rob M. Friedlander, Yechiel Koh, Woon-Puay Yuan, Jian-Min Khor, Chiea Chuen Heng, Chew-Kiat Dorajoo, Rajkumar Commun Biol Article The role of low frequency variants associated with telomere length homeostasis in chronic diseases and mortalities is relatively understudied in the East-Asian population. Here we evaluated low frequency variants, including 1,915,154 Asian specific variants, for leukocyte telomere length (LTL) associations among 25,533 Singapore Chinese samples. Three East Asian specific variants in/near POT1, TERF1 and STN1 genes are associated with LTL (Meta-analysis P 2.49×10(−14)–6.94×10(−10)). Rs79314063, a missense variant (p.Asp410His) at POT1, shows effect 5.3 fold higher and independent of a previous common index SNP. TERF1 (rs79617270) and STN1 (rs139620151) are linked to LTL-associated common index SNPs at these loci. Rs79617270 is associated with cancer mortality [HR(95%CI) = 1.544 (1.173, 2.032), P(Adj) = 0.018] and 4.76% of the association between the rs79617270 and colon cancer is mediated through LTL. Overall, genetically determined LTL is particularly associated with lung adenocarcinoma [HR(95%CI) = 1.123 (1.051, 1.201), P(adj) = 0.007]. Ethnicity-specific low frequency variants may affect LTL homeostasis and associate with certain cancers. Nature Publishing Group UK 2021-05-03 /pmc/articles/PMC8093266/ /pubmed/33941849 http://dx.doi.org/10.1038/s42003-021-02056-7 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Chang, Xuling Gurung, Resham L. Wang, Ling Jin, Aizhen Li, Zheng Wang, Renwei Beckman, Kenneth B. Adams-Haduch, Jennifer Meah, Wee Yang Sim, Kar Seng Lim, Weng Khong Davila, Sonia Tan, Patrick Teo, Jing Xian Yeo, Khung Keong M., Yiamunaa Liu, Sylvia Lim, Su Chi Liu, Jianjun van Dam, Rob M. Friedlander, Yechiel Koh, Woon-Puay Yuan, Jian-Min Khor, Chiea Chuen Heng, Chew-Kiat Dorajoo, Rajkumar Low frequency variants associated with leukocyte telomere length in the Singapore Chinese population |
title | Low frequency variants associated with leukocyte telomere length in the Singapore Chinese population |
title_full | Low frequency variants associated with leukocyte telomere length in the Singapore Chinese population |
title_fullStr | Low frequency variants associated with leukocyte telomere length in the Singapore Chinese population |
title_full_unstemmed | Low frequency variants associated with leukocyte telomere length in the Singapore Chinese population |
title_short | Low frequency variants associated with leukocyte telomere length in the Singapore Chinese population |
title_sort | low frequency variants associated with leukocyte telomere length in the singapore chinese population |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093266/ https://www.ncbi.nlm.nih.gov/pubmed/33941849 http://dx.doi.org/10.1038/s42003-021-02056-7 |
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