TY - JOUR
T1 - Low frequency variants associated with leukocyte telomere length in the Singapore Chinese population
AU - Chang, Xuling
AU - Gurung, Resham L.
AU - Wang, Ling
AU - Jin, Aizhen
AU - Li, Zheng
AU - Wang, Renwei
AU - Beckman, Kenneth B.
AU - Adams-Haduch, Jennifer
AU - Meah, Wee Yang
AU - Sim, Kar Seng
AU - Lim, Weng Khong
AU - Davila, Sonia
AU - Tan, Patrick
AU - Teo, Jing Xian
AU - Yeo, Khung Keong
AU - M, Yiamunaa
AU - Liu, Sylvia
AU - Lim, Su Chi
AU - Liu, Jianjun
AU - van Dam, Rob M.
AU - Friedlander, Yechiel
AU - Koh, Woon Puay
AU - Yuan, Jian Min
AU - Khor, Chiea Chuen
AU - Heng, Chew Kiat
AU - Dorajoo, Rajkumar
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85105243478
UR - https://www.scopus.com/pages/publications/85105243478#tab=citedBy
U2 - 10.1038/s42003-021-02056-7
DO - 10.1038/s42003-021-02056-7
M3 - Article
C2 - 33941849
AN - SCOPUS:85105243478
SN - 2399-3642
VL - 4
JO - Communications biology
JF - Communications biology
IS - 1
M1 - 519
ER -
