Relationship between genetically determined telomere length and glioma risk

Author:

Saunders Charlie N1ORCID,Kinnersley Ben1ORCID,Culliford Richard1,Cornish Alex J1,Law Philip J1,Houlston Richard S1

Affiliation:

1. Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK

Abstract

Abstract Background Telomere maintenance is increasingly recognized as being fundamental to glioma oncogenesis with longer leukocyte telomere length (LTL) reported to increase risk of glioma. To gain further insight into the relationship between telomere genetics and risk of glioma, we conducted several complementary analyses, using genome-wide association studies data on LTL (78 592 individuals) and glioma (12 488 cases and 18 169 controls). Methods We performed both classical and summary Mendelian randomization (SMR), coupled with heterogeneity in dependent instruments tests, at genome-wide significant LTL loci to examine if an association was mediated by the same causal variant in glioma. To prioritize genes underscoring glioma-LTL associations, we analyzed gene expression and DNA methylation data. Results Genetically increased LTL was significantly associated with increased glioma risk, random-effects inverse variance weighted ORs per 1 SD unit increase in the putative risk factor (odds ratio [OR]SD) 4.79 (95% confidence interval: 2.11-10.85; P = 1.76 × 10−4). SMR confirmed the previously reported LTL associations at 3q26.2 (TERC; PSMR = 1.33 × 10−5), 5p15.33 (TERT; PSMR = 9.80 × 10−27), 10q24.33 (STN1 alias OBFC1; PSMR = 4.31 × 10−5), and 20q13.3 (STMN3/RTEL1; PSMR = 2.47 × 10−4) glioma risk loci. Our analysis implicates variation at 1q42.12 (PSMR = 1.55 × 10−2), 6p21.3 (PSMR = 9.76 × 10−3), 6p22.2 (PSMR = 5.45 × 10−3), 7q31.33 (PSMR = 6.52 × 10−3), and 11q22.3 (PSMR = 8.89 × 10−4) as risk factors for glioma risk. While complicated by patterns of linkage disequilibrium, genetic variation involving PARP1, PRRC2A, CARMIL1, POT1, and ATM-NPAT1 was implicated in the etiology of glioma. Conclusions These observations extend the role of telomere-related genes in the development of glioma.

Funder

Cancer Research UK

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,Neurology (clinical),Oncology

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3