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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 <jats:italic>POT1<\/jats:italic>, <jats:italic>TERF1<\/jats:italic> and <jats:italic>STN1<\/jats:italic> genes are associated with LTL (Meta-analysis <jats:italic>P<\/jats:italic> 2.49\u00d710<jats:sup>\u221214<\/jats:sup>\u20136.94\u00d710<jats:sup>\u221210<\/jats:sup>). Rs79314063, a missense variant (p.Asp410His) at <jats:italic>POT1<\/jats:italic>, shows effect 5.3 fold higher and independent of a previous common index SNP. <jats:italic>TERF1<\/jats:italic> (rs79617270) and <jats:italic>STN1<\/jats:italic> (rs139620151) are linked to LTL-associated common index SNPs at these loci. Rs79617270 is associated with cancer mortality [HR<jats:sub>95%CI<\/jats:sub>\u2009=\u20091.544 (1.173, 2.032), <jats:italic>P<\/jats:italic><jats:sub>Adj<\/jats:sub>\u2009=\u20090.018] 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<jats:sub>95%CI<\/jats:sub>\u2009=\u20091.123 (1.051, 1.201), <jats:italic>P<\/jats:italic><jats:sub>adj<\/jats:sub>\u2009=\u20090.007]. Ethnicity-specific low frequency variants may affect LTL homeostasis and associate with certain cancers.<\/jats:p>","DOI":"10.1038\/s42003-021-02056-7","type":"journal-article","created":{"date-parts":[[2021,5,3]],"date-time":"2021-05-03T10:03:53Z","timestamp":1620036233000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Low frequency variants associated with leukocyte telomere length in the Singapore Chinese population"],"prefix":"10.1038","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7471-4768","authenticated-orcid":false,"given":"Xuling","family":"Chang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Resham 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