Searching for causal relationships of glioma: a phenome-wide Mendelian randomisation study.
Searching for causal relationships of glioma: a phenome-wide Mendelian randomisation study.
复制标题
DOI：
10.1038/s41416-020-01083-1
复制
发表时间：
2021-01
影响因子：
8.8
通讯作者：
Collaborators
中科院分区：
文献类型：
--
作者：
Saunders CN;Cornish AJ;Kinnersley B;Law PJ;Houlston RS;Collaborators
神经胶质瘤的病因学知之甚少。全基因组关联研究（GWAS）的总结数据可用于孟德尔随机化（MR）全表型关联研究（PheWAS），以搜索胶质瘤风险因素。我们进行了一项MR-PheWAS分析，分析了316种表型，由8387种遗传变异代表，并总结了来自12，488例胶质瘤病例和18，169例对照的GWAS的遗传数据。在随机效应逆方差加权（IVW-RE）模型下估计因果效应，计算稳健调整特征评分（MR-RAPS）、加权中位数和基于模式的估计值，以评估结果的稳健性。计算所有胶质瘤、胶质母细胞瘤（GBM）和非GBM肿瘤的每种表型每增加一个标准差的比值比。在IVW-RE模型下，没有观察到表型与胶质瘤之间的显著关联（P < 1.58 × 10−4）。在白细胞端粒长度（LTL）与所有胶质瘤（ORSD = 3.91，P = 9.24 × 10−3）和GBM（ORSD = 4.86，P = 3.23 × 10−2）之间观察到暗示性关联（1.58 × 10−4 < P < 0.05），但这种关联主要由TERT变体rs 2736100驱动。血清低密度脂蛋白胆固醇和血浆HbA 1C显示与胶质瘤相关（分别为ORSD = 1.11，P = 1.39 × 10−2和ORSD = 1.28，P = 1.73 × 10−2），这两种相关性都依赖于单一的遗传变异。我们的研究为神经胶质瘤的病因学基础提供了进一步的见解，而已发表的数据则是混合的。
The aetiology of glioma is poorly understood. Summary data from genome-wide association studies (GWAS) can be used in a Mendelian randomisation (MR) phenome-wide association study (PheWAS) to search for glioma risk factors. We performed an MR-PheWAS analysing 316 phenotypes, proxied by 8387 genetic variants, and summary genetic data from a GWAS of 12,488 glioma cases and 18,169 controls. Causal effects were estimated under a random-effects inverse-variance-weighted (IVW-RE) model, with robust adjusted profile score (MR-RAPS), weighted median and mode-based estimates computed to assess the robustness of findings. Odds ratios per one standard deviation increase in each phenotype were calculated for all glioma, glioblastoma (GBM) and non-GBM tumours. No significant associations (P < 1.58 × 10−4) were observed between phenotypes and glioma under the IVW-RE model. Suggestive associations (1.58 × 10−4 < P < 0.05) were observed between leukocyte telomere length (LTL) with all glioma (ORSD = 3.91, P = 9.24 × 10−3) and GBM (ORSD = 4.86, P = 3.23 × 10−2), but the association was primarily driven by the TERT variant rs2736100. Serum low-density lipoprotein cholesterol and plasma HbA1C showed suggestive associations with glioma (ORSD = 1.11, P = 1.39 × 10−2 and ORSD = 1.28, P = 1.73 × 10−2, respectively), both associations being reliant on single genetic variants. Our study provides further insight into the aetiological basis of glioma for which published data have been mixed.
登录
查看更多内容
影响因子：
8.8
作者：
Johansen C;Schüz J;Andreasen AS;Dalton SO
通讯作者：
Dalton SO
影响因子：
2.1
作者：
Bowden J;Davey Smith G;Haycock PC;Burgess S
通讯作者：
Burgess S
DOI：
10.1126/science.aaz6876
发表时间：
2020-09-11
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Demanelis K;Jasmine F;Chen LS;Chernoff M;Tong L;Delgado D;Zhang C;Shinkle J;Sabarinathan M;Lin H;Ramirez E;Oliva M;Kim-Hellmuth S;Stranger BE;Lai TP;Aviv A;Ardlie KG;Aguet F;Ahsan H;GTEx Consortium;Doherty JA;Kibriya MG;Pierce BL
通讯作者：
Pierce BL
影响因子：
7.7
作者：
Brion, Marie-Jo A.;Shakhbazov, Konstantin;Visscher, Peter M.
通讯作者：
Visscher, Peter M.
DOI：
10.1080/01635581.2011.523807
发表时间：
2011
期刊：
Nutrition and cancer
影响因子：
--
作者：
Kyritsis AP;Bondy ML;Levin VA
通讯作者：
Levin VA