biostudies-literatureChang XNCI NIH HHS519https://www.ebi.ac.uk/biostudies/studies/S-EPMC8093266biostudies-literatureUnknown4(1)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.Communications biologyLow frequency variants associated with leukocyte telomere length in the Singapore Chinese population.PMC8093266R01 CA144034UM1 CA182876Liu JDorajoo RM YAdams-Haduch JLiu SWang LKoh WPJin AWang RDavila SKhor CCMeah WYGurung RLYuan JMHeng CKTeo JXSim KSLim SCvan Dam RMChang XLim WKBeckman KBLi ZTan PYeo KKFriedlander YfalseLow 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) 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.2021-01-01T00:00:00Z2021 May2026-05-08T07:04:20.781Z2025-02-19T00:17:19.818ZS-EPMC80932663394184910.1038/s42003-021-02056-7