Tan Xingling, Xiao Zhouyouyou, Wen Yao, Liu Han, Yu Wei
Institute of Life Science, Chongqing Medical University, Chongqing, China.
Department of Audiology and Speech Rehabilitation, Chongqing Medical University, Chongqing, China.
World Allergy Organ J. 2024 Dec 19;18(1):101014. doi: 10.1016/j.waojou.2024.101014. eCollection 2025 Jan.
Allergic rhinitis (AR) is a common chronic respiratory disease that can lead to the development of various other conditions. Although genetic risk loci associated with AR have been reported, the connections between these loci and AR comorbidities or other diseases remain unclear.
This study conducted a phenome-wide association study (PheWAS) using known AR risk loci to explore the impact of known AR risk variants on a broad spectrum of phenotypes. Subsequently, linkage disequilibrium score regression (LDSC) and bidirectional two-sample mendelian randomization (TSMR) analyses were used to further analyze the genetic correlation and causal relationships between significant and potentially related phenotypes and AR.
The PheWAS analysis indicated significant associations between asthma, eczema, nasal polyps, hypothyroidism, and AR risk variants. Additionally, potential associations were observed with ulcerative colitis, psoriasis, chalazion, pernicious anemia, glaucoma, multiple sclerosis, arthritis, prostate cancer, varicose veins of lower extremities, and heart attack. LDSC analysis showed that only asthma, eczema, and nasal polyps have significant positive genetic correlations with AR. Furthermore, TSMR analysis revealed causal relationships between AR and asthma, eczema, and nasal polyps.
This study highlights the impact of AR risk loci on a variety of diseases. By revealing new associations and shared genetic pathways, our findings provide valuable insights into the pathophysiology of AR and pave the way for more effective targeted interventions to manage AR and its related diseases.
变应性鼻炎（AR）是一种常见的慢性呼吸道疾病，可导致多种其他疾病的发生。尽管已报道了与AR相关的遗传风险位点，但这些位点与AR合并症或其他疾病之间的联系仍不清楚。
本研究使用已知的AR风险位点进行全表型关联研究（PheWAS），以探索已知的AR风险变异对广泛表型的影响。随后，使用连锁不平衡评分回归（LDSC）和双向双样本孟德尔随机化（TSMR）分析进一步分析显著和潜在相关表型与AR之间的遗传相关性和因果关系。
PheWAS分析表明哮喘、湿疹、鼻息肉、甲状腺功能减退与AR风险变异之间存在显著关联。此外，还观察到与溃疡性结肠炎、银屑病、睑板腺囊肿、恶性贫血、青光眼、多发性硬化症、关节炎、前列腺癌、下肢静脉曲张和心脏病发作之间存在潜在关联。LDSC分析表明，只有哮喘、湿疹和鼻息肉与AR有显著的正遗传相关性。此外，TSMR分析揭示了AR与哮喘、湿疹和鼻息肉之间的因果关系。
本研究强调了AR风险位点对多种疾病的影响。通过揭示新的关联和共享的遗传途径，我们的发现为AR的病理生理学提供了有价值的见解，并为更有效的针对性干预措施管理AR及其相关疾病铺平了道路。
