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阐明哮喘和肥胖之间的因果关系:一项双向孟德尔随机化研究。

Elucidation of causal direction between asthma and obesity: a bi-directional Mendelian randomization study.

机构信息

Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

出版信息

Int J Epidemiol. 2019 Jun 1;48(3):899-907. doi: 10.1093/ije/dyz070.


DOI:10.1093/ije/dyz070
PMID:31005996
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6659368/
Abstract

BACKGROUND: Observational associations between asthma and obesity are well established, but inferring causality is challenging. We leveraged publicly available summary statistics to ascertain the causal direction between asthma and obesity via Mendelian randomization in European-ancestry adults. METHODS: We performed two-sample bi-directional Mendelian randomization analysis using publicly available genome-wide association studies summary statistics. Single nucleotide polymorphisms associated with asthma and body mass index at genome-wide significance were combined using a fixed effect meta-analysis in each direction. An extensive sensitivity analysis was considered. RESULTS: There was evidence in support of increasing causal effect of body mass index on risk of asthma (odds ratio 1.18 per unit increase, 95% confidence interval (CI) (1.11, 1.25), P = 2 × 10-8. No significant causal effect of asthma on adult body mass index was observed [estimate -0.004, 95% CI (-0.018, 0.009), P = 0.553]. CONCLUSIONS: Our results confirmed that in European-ancestry populations, adult body mass index is likely to be causally linked to the risk of asthma; yet the effect of asthma on body mass index is small, if present at all.

摘要

背景:哮喘和肥胖之间的观察性关联已得到充分证实,但推断因果关系具有挑战性。我们利用公开可用的汇总统计数据,通过欧洲血统成年人的孟德尔随机化来确定哮喘和肥胖之间的因果关系方向。

方法:我们使用公开的全基因组关联研究汇总统计数据进行了两样本双向孟德尔随机化分析。使用固定效应荟萃分析在每个方向上组合与哮喘和体重指数具有全基因组显着性关联的单核苷酸多态性。考虑了广泛的敏感性分析。

结果:有证据支持体重指数对哮喘风险的因果影响增加(每单位增加 1.18 的优势比,95%置信区间(CI)(1.11,1.25),P = 2 × 10-8。未观察到哮喘对成人体重指数的显着因果影响[估计值 -0.004,95%CI(-0.018,0.009),P = 0.553]。

结论:我们的结果证实,在欧洲血统人群中,成人体重指数可能与哮喘风险存在因果关系;然而,哮喘对体重指数的影响很小,如果存在的话。

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本文引用的文献

[1]
Distinguishing genetic correlation from causation across 52 diseases and complex traits.

Nat Genet. 2018-10-29

[2]
Causal relationships between adiposity and childhood asthma: bi-directional Mendelian Randomization analysis.

Int J Obes (Lond). 2018-7-19

[3]
Heterogeneity and the origins of asthma.

Ann Allergy Asthma Immunol. 2018-6-19

[4]
Mixed-model association for biobank-scale datasets.

Nat Genet. 2018-7

[5]
Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases.

Nat Genet. 2018-4-23

[6]
Obesity and asthma.

J Allergy Clin Immunol. 2018-4

[7]
Transformation of Summary Statistics from Linear Mixed Model Association on All-or-None Traits to Odds Ratio.

Genetics. 2018-2-2

[8]
Lessons from ten years of genome-wide association studies of asthma.

Clin Transl Immunology. 2017-12-15

[9]
Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks.

Nat Genet. 2017-12-22

[10]
Mendelian Randomization.

JAMA. 2017-11-21

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