Targeted resequencing showing novel common and rare genetic variants increases the risk of asthma in the Chinese Han population. Issue 6 (9th May 2021)

• Record Type: Journal Article
• Authors: Liu, Juan; Deng, Yanhan; Yu, Bo; Mo, Biwen; Luo, Liman; Yang, Jingping; Zhang, Xiaoju; Wang, Zheng; Wang, Yingnan; Zhu, Jing; Yang, Hua; Fang, Shirong; Cheng, Zhenshun; Li, Jingping; Shu, Ying; Luo, Guangwei; Xiong, Weining; Wei, Jianghong; Li, Zongzhe
• Is Part Of: Journal of clinical laboratory analysis. Volume 35:Issue 6(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-05-09
• Subjects: asthma -- common variant -- next‐generation sequencing -- rare variant -- risk stratification; Diagnosis, Laboratory -- Periodicals; Medical laboratory technology -- Periodicals; 616
• DOI: 10.1002/jcla.23813
• Languages: English
• ISSNs: 0887-8013

Abstract

Abstract: Background: Although studies have identified hundreds of genetic variants associated with asthma risk, a large fraction of heritability remains unexplained, especially in Chinese individuals. Methods: To identify genetic risk factors for asthma in a Han Chinese population, 211 asthma‐related genes were first selected based on database searches. The genes were then sequenced for subjects in a Discovery Cohort (284 asthma patients and 205 older healthy controls) using targeted next‐generation sequencing. Bioinformatics analysis and statistical association analyses were performed to reveal the associations between rare/common variants and asthma, respectively. The identified common risk variants underwent a validation analysis using a Replication Cohort (664 patients and 650 controls). Results: First, we identified 18 potentially functional rare loss‐of‐function (LOF) variants in 21/284 (7.4%) of the asthma cases. Second, using burden tests, we found that the asthma group had nominally significant ( p < 0.05) burdens of rare nonsynonymous variants in 10 genes. Third, 23 common single‐nucleotide polymorphisms were associated with the risk of asthma, 7/23 (30.4%) and 9/23 (39.1%) of which were modestly significant ( p < 9.1 × 10 −4 ) in the Replication Cohort and Combined Cohort, respectively. According to our cumulative risk model involving the modestly associated alleles, middle‐ and high‐risk subjects had a 2.0‐fold (95% CI: 1.621–2.423, p = 2.624 × 10 −11 ) and 6.0‐fold (95% CI: 3.623–10.156, p = 7.086 × 10 −12 ) increased risk of asthma, respectively, compared with low‐risk subjects. Conclusion: This study revealed novel rare and common genetic risk factors for asthma, and provided a cumulative risk model for asthma risk prediction and stratification in Han Chinese individuals. Abstract : To identify genetic risk factors for asthma in a Han Chinese population, 211 asthma‐related genes were sequenced in a Discovery Cohort and then identified common risk variants underwent a validation analysis using a Replication Cohort. Association analysis and subgroup analysis showed 17 of the SNPs were nominally associated with childhood‐onset asthma, 13 with adolescent/young adult‐onset asthma, and only seven with adult‐onset asthma.