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一项关于新冠病毒病对女性特定癌症影响的大规模全基因组跨性状分析。

A large-scale genome-wide cross-trait analysis for the effect of COVID-19 on female-specific cancers.

作者信息

Zhao Xunying, Wu Xueyao, Xiao Jinyu, Zhang Li, Hao Yu, Xiao Chenghan, Zhang Ben, Li Jiayuan, Jiang Xia

机构信息

Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.

Department of Maternal, Child and Adolescent Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.

出版信息

iScience. 2023 Jul 29;26(9):107497. doi: 10.1016/j.isci.2023.107497. eCollection 2023 Sep 15.

DOI:10.1016/j.isci.2023.107497
PMID:37636041
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10450412/
Abstract

Little is known regarding the long-term adverse effects of COVID-19 on female-specific cancers, nor the shared genetic influences underlying these conditions. We performed a comprehensive genome-wide cross-trait analysis to investigate the shared genetic architecture between COVID-19 (infection, hospitalization, and critical illness) with three female-specific cancers (breast cancer (BC), epithelial ovarian cancer (EOC), and endometrial cancer (EC)). We identified significant genome-wide genetic correlations with EC for both hospitalization ( = 0.19, p = 0.01) and critical illness ( = 0.29, p = 3.00 × 10). Mendelian randomization demonstrated no valid association of COVID-19 with any cancer of interest, except for suggestive associations of genetically predicted hospitalization (OR = 1.09, p = 0.04) and critical illness (OR = 1.06, p = 0.04) with EC risk, none withstanding multiple correction. Cross-trait meta-analysis identified 20 SNPs shared between COVID-19 with BC, 15 with EOC, and 5 with EC; and transcriptome-wide association studies revealed multiple shared genes. Findings support intrinsic links underlying these complex traits, highlighting shared mechanisms rather than causal associations.

摘要

关于新冠病毒病对女性特定癌症的长期不良影响，以及这些疾病背后的共同遗传影响，我们所知甚少。我们进行了一项全面的全基因组跨性状分析，以研究新冠病毒病（感染、住院和危重症）与三种女性特定癌症（乳腺癌（BC）、上皮性卵巢癌（EOC）和子宫内膜癌（EC））之间的共同遗传结构。我们发现，住院（r = 0.19，p = 0.01）和危重症（r = 0.29，p = 3.00×10⁻⁴）与子宫内膜癌均存在全基因组显著遗传相关性。孟德尔随机化分析表明，除了遗传预测的住院（OR = 1.09，p = 0.04）和危重症（OR = 1.06，p = 0.04）与子宫内膜癌风险存在提示性关联外，新冠病毒病与任何感兴趣的癌症均无有效关联，尽管进行了多次校正。跨性状荟萃分析确定了新冠病毒病与乳腺癌之间共享的20个单核苷酸多态性（SNP）、与上皮性卵巢癌之间共享的15个SNP以及与子宫内膜癌之间共享的5个SNP；全转录组关联研究揭示了多个共享基因。研究结果支持了这些复杂性状背后的内在联系，突出了共享机制而非因果关联。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32f8/10450412/542a3823f370/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32f8/10450412/dfed02a2b5dc/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32f8/10450412/c58a73e61b8d/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32f8/10450412/c85d33322de3/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32f8/10450412/542a3823f370/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32f8/10450412/dfed02a2b5dc/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32f8/10450412/c58a73e61b8d/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32f8/10450412/c85d33322de3/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32f8/10450412/542a3823f370/gr3.jpg

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