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

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

doi:10.1016/j.isci.2023.107497

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

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

Authors

Xunying Zhao¹, Xueyao Wu¹, Jinyu Xiao¹, Li Zhang¹, Yu Hao¹, Chenghan Xiao², Ben Zhang^{1

3}, Jiayuan Li¹, Xia Jiang^{1

4

5

6}

Affiliations

¹ 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.
² Department of Maternal, Child and Adolescent Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
³ Department of Occupational and Environmental Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
⁴ Department of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
⁵ Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, Solna, Stockholm, Sweden.
⁶ Program in Genetic Epidemiology and Statistical Genetics, Harvard T. H. Chan School of Public Health, Boston, MA, USA.

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 ( $r_{g}$ = 0.19, p = 0.01) and critical illness ( $r_{g}$ = 0.29, p = 3.00 × 10^-4). Mendelian randomization demonstrated no valid association of COVID-19 with any cancer of interest, except for suggestive associations of genetically predicted hospitalization (OR_IVW = 1.09, p = 0.04) and critical illness (OR_IVW = 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.

Keywords: Cancer; Public health; Virology.