Low frequency variants associated with leukocyte telomere length in the Singapore Chinese population

被引：17

作者：

Chang, Xuling ^{[1
,2
]}

Gurung, Resham L. ^{[3
]}

Wang, Ling ^{[4
]}

Jin, Aizhen ^{[5
]}

Li, Zheng ^{[4
]}

Wang, Renwei ^{[6
]}

Beckman, Kenneth B. ^{[7
]}

Adams-Haduch, Jennifer ^{[6
]}

Meah, Wee Yang ^{[4
]}

Sim, Kar Seng ^{[4
]}

Lim, Weng Khong ^{[8
,9
,10
]}

Davila, Sonia ^{[8
,11
]}

Tan, Patrick ^{[4
,8
,9
,12
]}

Teo, Jing Xian ^{[8
]}

Yeo, Khung Keong ^{[8
,13
]}

Yiamunaa, M. ^{[3
]}

Liu, Sylvia ^{[3
]}

Lim, Su Chi ^{[3
,14
,15
]}

Liu, Jianjun ^{[4
,16
]}

van Dam, Rob M. ^{[15
,16
]}

Friedlander, Yechiel ^{[17
]}

Koh, Woon-Puay ^{[5
,15
]}

Yuan, Jian-Min ^{[6
,18
]}

Khor, Chiea Chuen ^{[4
,19
]}

Heng, Chew-Kiat ^{[1
,2
]}

Dorajoo, Rajkumar ^{[4
,5
]}

机构：

[1] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Paediat, Singapore, Singapore

[2] Natl Univ Hlth Syst, Khoo Teck Puat Natl Univ Childrens Med Inst, Singapore, Singapore

[3] Khoo Teck Puat Hosp, Clin Res Unit, Singapore, Singapore

[4] Agcy Sci Technol & Res, Genome Inst Singapore, Singapore, Singapore

[5] Duke NUS Med Sch Singapore, Hlth Serv & Syst Res, Singapore, Singapore

[6] Univ Pittsburgh, UPMC Hillman Canc Ctr, Div Canc Control & Populat Sci, Pittsburgh, PA USA

[7] Univ Minnesota, Genom Ctr, Minneapolis, MN USA

[8] SingHlth Duke NUS Inst Precis Med, Singapore, Singapore

[9] Duke NUS Med Sch, Canc & Stem Cell Biol Program, Singapore, Singapore

[10] SingHlth Duke NUS Genom Med Ctr, Singapore, Singapore

[11] Duke NUS Med Sch, Cardiovasc & Metab Disorders Program, Singapore, Singapore

[12] Natl Univ Singapore, Canc Sci Inst Singapore, Singapore, Singapore

[13] Natl Heart Ctr Singapore, Dept Cardiol, Singapore, Singapore

[14] Admiralty Med Ctr, Diabet Ctr, Singapore, Singapore

[15] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore

[16] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore, Singapore

[17] Hebrew Univ Jerusalem, Sch Publ Hlth & Community Med, Jerusalem, Israel

[18] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA

[19] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore

来源：

COMMUNICATIONS BIOLOGY | 2021年 / 4卷 / 01期

基金：

美国国家卫生研究院; 英国医学研究理事会; 新加坡国家研究基金会;

关键词：

GENOME-WIDE ASSOCIATION; IDENTIFIES RARE VARIANTS; CORONARY-HEART-DISEASE; CANCER; RISK; IMPUTATION; HERITABILITY; SMOKING; HEALTH; POT1;

D O I：

10.1038/s42003-021-02056-7

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 2.49x10(-14)-6.94x10(-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), 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 [HR95%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. Xuling Chang et al. study whether low frequency variants are associated with leukocyte telomere length and whether these variants predispose to incident cancers and mortalities among East Asians. They find that three East Asian specific variants at POT1, TERF1 and STN1 loci are associated with leukocyte telomere length and report a mechanistic pathway linking TERF1, leukocyte telomere length and incident colon cancer.

引用

页数：9

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