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Fine mapping in TERT‐CLPTM1L region identified three independent lung cancer susceptibility signals: A large‐scale multi‐ethnic population study
Author(s) -
Li Zhihua,
Pu Zhening,
Fan Jingyi,
Li Ni,
Zhu Meng,
Zhang Jiahui,
Wang Yuzhuo,
Geng Liguo,
Cheng Yang,
Ma Hongxia,
Jin Guangfu,
Dai Juncheng,
Hu Zhibin,
Shen Hongbing
Publication year - 2018
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22843
Subject(s) - lung cancer , biology , lung cancer susceptibility , genome wide association study , population , genetics , single nucleotide polymorphism , oncology , genotype , medicine , gene , environmental health
Genome‐wide association studies (GWAS) and fine mapping studies have identified multiple lung cancer susceptibility variants in TERT‐CLPTM1L region. However, it is still unclear about the relationship between these risk variants and the independent lung cancer risk signals in this region. Therefore, we evaluated the independent susceptibility signals for lung cancer and explored the potential functional variants in this region. Sequential conditional analysis was used to detect the independent susceptibility loci based on four lung cancer GWAS datasets with 12 843 lung cases and 12 639 controls. Comprehensively functional annotations were performed for each independent signal. Three independent susceptibility signals were identified in multi‐ethnic population. For the first signal, rs2736100 showed the most significant association with lung cancer risk (C > A, OR = 0.82, 95%CI: 0.79‐0.85, P = 1.98 × 10 −25 ). Rs36019446 was the top‐ranked site (A > G, OR = 0.88, 95%CI: 0.84‐0.92, P = 1.74 × 10 −9 ) in the second signal. For the third signal, rs326048 was the leading SNP (A > G, OR = 0.91, 95%CI: 0.87‐0.95, P = 1.38 × 10 −5 ). The following subgroup analysis found the same three loci among Asian population. Further, we compared the difference between various subgroup populations. Functional annotations revealed that rs2736100, rs27996 ( r 2 = 0.85 with rs36019446) and rs326049 ( r 2 = 0.73 with rs326048) could be potential functional variants in these three risk signals, respectively. In conclusion, although multiple variants have been found associated with lung cancer risk in TERT‐CLPTM1L region, our findings indicated that there are three independent lung cancer susceptibility signals in this region.