Guo Hongping, An Jiyuan, Yu Zuguo
Key Laboratory of Intelligent Computing and Information Processing of Ministry of Education and Hunan Key Laboratory for Computation and Simulation in Science and Engineering, Xiangtan University, Hunan, China.
School of Mathematics and Computer Science, Hanjiang Normal University, Hubei, China.
Front Genet. 2020 Apr 16;11:270. doi: 10.3389/fgene.2020.00270. eCollection 2020.
Asthma, hay fever and eczema are three comorbid diseases with high prevalence and heritability. Their common genetic architectures have not been well-elucidated. In this study, we first conducted a linkage disequilibrium score regression analysis to confirm the strong genetic correlations between asthma, hay fever and eczema. We then integrated three distinct association analyses (metaCCA multi-trait association analysis, MAGMA genome-wide and MetaXcan transcriptome-wide gene-based tests) to identify shared risk genes based on the large-scale GWAS results in the GeneATLAS database. MetaCCA can detect pleiotropic genes associated with these three diseases jointly. MAGMA and MetaXcan were performed separately to identify candidate risk genes for each of the three diseases. We finally identified 150 shared risk genes, in which 60 genes are novel. Functional enrichment analysis revealed that the shared risk genes are enriched in inflammatory bowel disease, T cells differentiation and other related biological pathways. Our work may provide help on treatment of asthma, hay fever and eczema in clinical applications.
哮喘、花粉症和湿疹是三种高发性和遗传性的共病。它们共同的遗传结构尚未得到充分阐明。在本研究中，我们首先进行了连锁不平衡评分回归分析，以确认哮喘、花粉症和湿疹之间存在很强的遗传相关性。然后，我们整合了三种不同的关联分析（metaCCA多性状关联分析、MAGMA全基因组分析和MetaXcan全转录组基因检测），以基于GeneATLAS数据库中的大规模全基因组关联研究（GWAS）结果识别共享风险基因。MetaCCA可以联合检测与这三种疾病相关的多效性基因。分别进行MAGMA和MetaXcan分析以识别这三种疾病各自的候选风险基因。我们最终鉴定出150个共享风险基因，其中60个基因为新发现的基因。功能富集分析表明，共享风险基因在炎症性肠病、T细胞分化和其他相关生物学途径中富集。我们的工作可能会在临床应用中为哮喘、花粉症和湿疹的治疗提供帮助。
