Using multi-tissue transcriptome-wide association study to identify candidate susceptibility genes for respiratory infectious diseases

Xiaobo Zhu; Yixin Zou; Linna Jia; Xiangyu Ye; Yanzheng Zou; Junlan Tu; Juntong Li; Rongbin Yu; Sheng Yang; Peng Huang

doi:10.3389/fgene.2023.1164274

Using multi-tissue transcriptome-wide association study to identify candidate susceptibility genes for respiratory infectious diseases

Front Genet. 2023 Mar 20:14:1164274. doi: 10.3389/fgene.2023.1164274. eCollection 2023.

Authors

Xiaobo Zhu¹, Yixin Zou², Linna Jia², Xiangyu Ye², Yanzheng Zou², Junlan Tu², Juntong Li², Rongbin Yu², Sheng Yang³, Peng Huang²

Affiliations

¹ The People's Hospital of Danyang, Affiliated Danyang Hospital of Nantong University, Zhenjiang, China.
² Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.
³ Department of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.

Abstract

Objective: We explore the candidate susceptibility genes for influenza A virus (IAV), measles, rubella, and mumps and their underlying biological mechanisms. Methods: We downloaded the genome-wide association study summary data of four virus-specific immunoglobulin G (IgG) level data sets (anti-IAV IgG, anti-measles IgG, anti-rubella IgG, and anti-mumps virus IgG levels) and integrated them with reference models of three potential tissues from the Genotype-Tissue Expression (GTEx) project, namely, whole blood, lung, and transformed fibroblast cells, to identify genes whose expression is predicted to be associated with IAV, measles, mumps, and rubella. Results: We identified 19 significant genes (ULK4, AC010132.11, SURF1, NIPAL2, TRAP1, TAF1C, AC000078.5, RP4-639F20.1, RMDN2, ATP1B3, SRSF12, RP11-477D19.2, TFB1M, XXyac-YX65C7_A.2, TAF1C, PCGF2, and BNIP1) associated with IAV at a Bonferroni-corrected threshold of p < 0.05; 14 significant genes (SOAT1, COLGALT2, AC021860.1, HCG11, METTL21B, MRPL10, GSTM4, PAQR6, RP11-617D20.1, SNX8, METTL21B, ANKRD27, CBWD2, and TSFM) associated with measles at a Bonferroni-corrected threshold of p < 0.05; 15 significant genes (MTOR, LAMC1, TRIM38, U91328.21, POLR2J, SCRN2, Smpd4, UBN1, CNTROB, SCRN2, HOXB-AS1, SLC14A1, AC007566.10, AC093668.2, and CPD) associated with mumps at a Bonferroni-corrected threshold of p < 0.05; and 13 significant genes (JAGN1, RRP12, RP11-452K12.7, CASP7, AP3S2, IL17RC, FAM86HP, AMACR, RRP12, PPP2R1B, C11orf1, DLAT, and TMEM117) associated with rubella at a Bonferroni-corrected threshold of p < 0.05. Conclusions: We have identified several candidate genes for IAV, measles, mumps, and rubella in multiple tissues. Our research may further our understanding of the pathogenesis of infectious respiratory diseases.

Keywords: IAV; gene expression; genome-wide association studies; measles; multiple tissues; mumps; rubella; transcriptome-wide association study.

Grants and funding

This study was sponsored by the National Natural Science Foundation of China (82173585 and 82273741), the Natural Science Foundation of Jiangsu Province (BK20190106), and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).