| Literature DB >> 33941849 |
Xuling Chang1,2, Resham L Gurung3, Ling Wang4, Aizhen Jin5, Zheng Li4, Renwei Wang6, Kenneth B Beckman7, Jennifer Adams-Haduch6, Wee Yang Meah4, Kar Seng Sim4, Weng Khong Lim8,9,10, Sonia Davila8,11, Patrick Tan4,8,9,12, Jing Xian Teo8, Khung Keong Yeo8,13, Yiamunaa M3, Sylvia Liu3, Su Chi Lim3,14,15, Jianjun Liu4,16, Rob M van Dam15,16, Yechiel Friedlander17, Woon-Puay Koh5,15, Jian-Min Yuan6,18, Chiea Chuen Khor4,19, Chew-Kiat Heng20,21, Rajkumar Dorajoo22,23.
Abstract
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 [HR95%CI = 1.544 (1.173, 2.032), PAdj = 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 [HR95%CI = 1.123 (1.051, 1.201), Padj = 0.007]. Ethnicity-specific low frequency variants may affect LTL homeostasis and associate with certain cancers.Entities:
Year: 2021 PMID： 33941849 DOI： 10.1038/s42003-021-02056-7
Source DB: PubMed Journal: Commun Biol ISSN： 2399-3642