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10.1002-jcla.23813 |
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220427s2021 CNT 000 0 und d |
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|a 08878013 (ISSN)
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|a Targeted resequencing showing novel common and rare genetic variants increases the risk of asthma in the Chinese Han population
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|b John Wiley and Sons Inc
|c 2021
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|z View Fulltext in Publisher
|u https://doi.org/10.1002/jcla.23813
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|a 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. © 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC
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|a adolescent
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|a Adolescent
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|a adult
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|a Adult
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|a aged
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|a Aged
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|a Aged, 80 and over
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|a Article
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|a asthma
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|a asthma
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|a asthma
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|a Asthma
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|a bioinformatics
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|a biological marker
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|a Biomarkers
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|a case control study
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|a Case-Control Studies
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|a child
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|a Child
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|a Child, Preschool
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|a China
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|a China
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|a cohort analysis
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|a Cohort Studies
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|a common variant
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|a controlled study
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|a female
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|a Female
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|a follow up
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|a Follow-Up Studies
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|a gene frequency
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|a gene interaction
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|a gene sequence
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|a genetic predisposition
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|a Genetic Predisposition to Disease
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|a genetic risk
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|a genetic selection
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|a genetic variability
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|a genetics
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|a genome-wide association study
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|a Genome-Wide Association Study
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|a genotype
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|a Han Chinese
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|a high throughput sequencing
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|a High-Throughput Nucleotide Sequencing
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|a human
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|a Humans
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|a infant
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|a Infant
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|a Infant, Newborn
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|a loss of function mutation
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|a major clinical study
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|a male
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|a Male
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|a metabolism
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|a middle aged
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|a Middle Aged
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|a newborn
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|a next-generation sequencing
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|a pathology
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|a Polymorphism, Single Nucleotide
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|a population research
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|a preschool child
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|a procedures
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|a prognosis
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|a Prognosis
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|a rare variant
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|a risk factor
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|a risk stratification
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|a Sanger sequencing
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|a single nucleotide polymorphism
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|a single nucleotide polymorphism
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|a very elderly
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|a young adult
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|a Young Adult
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|a Cheng, Z.
|e author
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|a Deng, Y.
|e author
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|a Fang, S.
|e author
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|a Li, J.
|e author
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|a Li, Z.
|e author
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|a Liu, J.
|e author
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|a Luo, G.
|e author
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|a Luo, L.
|e author
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|a Mo, B.
|e author
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|a Shu, Y.
|e author
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|a Wang, Y.
|e author
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|a Wang, Z.
|e author
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|a Wei, J.
|e author
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|a Xiong, W.
|e author
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|a Yang, H.
|e author
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|a Yang, J.
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|a Yu, B.
|e author
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|a Zhang, X.
|e author
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|a Zhu, J.
|e author
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|t Journal of Clinical Laboratory Analysis
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