| Title: |
Low frequency variants associated with leukocyte telomere length in the Singapore Chinese population |
| Authors: |
Chang, X; Gurung, RL; Wang, L; Jin, A; Li, Z; Wang, R; Beckman, KB; Adams-Haduch, J; Meah, WY; Sim, KS; Lim, WK; Davila, S; Tan, P; Teo, JX; Yeo, KK; M, Y; Liu, S; Lim, SC; Liu, J; van Dam, RM; Friedlander, Y; Koh, WP; Yuan, JM; Khor, CC; Heng, CK; Dorajoo, R |
| Publisher Information: |
Springer Science and Business Media LLC |
| Publication Year: |
2021 |
| Collection: |
The University of Melbourne: Digital Repository |
| 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 [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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
2399-3642 |
| Relation: |
https://hdl.handle.net/11343/278178 |
| Availability: |
https://hdl.handle.net/11343/278178 |
| Rights: |
https://creativecommons.org/licenses/by/4.0 ; CC BY |
| Accession Number: |
edsbas.59AC8774 |
| Database: |
BASE |