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遗传变异、肥胖特征与台湾生物银行人群哮喘的关系。

Relationship among genetic variants, obesity traits and asthma in the Taiwan Biobank.

机构信息

Research Center for Humanities and Social Sciences, Academia Sinica, Taipei City, Taiwan.

Institute of Statistical Science, Academia Sinica, Taipei City, Taiwan.

出版信息

BMJ Open Respir Res. 2022 Dec;9(1). doi: 10.1136/bmjresp-2022-001355.

Abstract

BACKGROUND AND OBJECTIVE

Obesity and asthma impose a heavy health and economic burden on millions of people around the world. The complex interaction between genetic traits and phenotypes caused the mechanism between obesity and asthma is still vague. This study investigates the relationship among obesity-related polygenic risk score (PRS), obesity phenotypes and the risk of having asthma.

METHODS

This is a matched case-control study, with 4 controls (8288 non-asthmatic) for each case (2072 asthmatic). Data were obtained from the 2008-2015 Taiwan Biobank Database and linked to the 2000-2016 National Health Insurance Research Database. All participants were ≥30 years old with no history of cancer and had a complete questionnaire, as well as physical examination, genome-wide single nucleotide polymorphisms and clinical diagnosis data. Environmental exposure, PM, was also considered. Multivariate adjusted ORs and 95% CIs were calculated using conditional logistic regression stratified by age and sex. Mediation analysis was also assessed, using a generalised linear model.

RESULTS

We found that the obese phenotype was associated with significantly increased odds of asthma by approximately 26%. Four obesity-related PRS, including body mass index (OR=1.07 (1.01-1.13)), waist circumference (OR=1.10 (1.04-1.17)), central obesity as defined by waist-to-height ratio (OR=1.09 (1.03-1.15)) and general-central obesity (OR=1.06 (1.00-1.12)), were associated with increased odds of asthma. Additional independent risk factors for asthma included lower educational level, family history of asthma, certain chronic diseases and increased PM exposure. Obesity-related PRS is an indirect risk factor for asthma, the link being fully mediated by the trait of obesity.

CONCLUSIONS

Obese phenotypes and obesity-related PRS are independent risk factors for having asthma in adults in the Taiwan Biobank. Overall, genetic risk for obesity increases the risk of asthma by affecting the obese phenotype.

摘要

背景和目的

肥胖和哮喘给全世界数以百万计的人带来了沉重的健康和经济负担。遗传特征和表型之间的复杂相互作用导致肥胖和哮喘之间的机制仍不清楚。本研究调查了肥胖相关多基因风险评分(PRS)、肥胖表型与哮喘风险之间的关系。

方法

这是一项匹配的病例对照研究,每个病例(2072 例哮喘)匹配 4 个对照(8288 例非哮喘)。数据来自 2008-2015 年台湾生物库数据库,并与 2000-2016 年国家健康保险研究数据库相关联。所有参与者年龄均≥30 岁,无癌症病史,且完成了问卷、体检、全基因组单核苷酸多态性和临床诊断数据。还考虑了环境暴露因素 PM。使用条件逻辑回归,按年龄和性别分层,计算多变量调整后的 OR 和 95%CI。使用广义线性模型评估中介分析。

结果

我们发现肥胖表型与哮喘的发生风险显著增加约 26%有关。四个肥胖相关的 PRS,包括体重指数(OR=1.07(1.01-1.13))、腰围(OR=1.10(1.04-1.17))、腰高比定义的中心性肥胖(OR=1.09(1.03-1.15))和全身性中心性肥胖(OR=1.06(1.00-1.12)),与哮喘的发生风险增加有关。哮喘的其他独立危险因素包括较低的教育水平、哮喘家族史、某些慢性疾病和 PM 暴露增加。肥胖相关的 PRS 是哮喘的一个间接危险因素,这种联系完全由肥胖表型介导。

结论

肥胖表型和肥胖相关的 PRS 是台湾生物库中成年人患哮喘的独立危险因素。总体而言,肥胖的遗传风险通过影响肥胖表型增加了哮喘的风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/096f/9730389/02eb9e9f4874/bmjresp-2022-001355f01.jpg

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