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. 2023 Jul;87(4):174-183.
doi: 10.1111/ahg.12506. Epub 2023 Apr 3.

The impact of obesity on lung function measurements and respiratory disease: A Mendelian randomization study

Jiayan Liu  1 , Hanfei Xu  2 , L Adrienne Cupples  2 , George T O' Connor  3   4 , Ching-Ti Liu  2
Affiliations

The impact of obesity on lung function measurements and respiratory disease: A Mendelian randomization study

Jiayan Liu et al. Ann Hum Genet. 2023 Jul.

Abstract

Introduction: Observational studies have shown that body mass index (BMI) and waist-to-hip ratio (WHR) are both inversely associated with lung function, as assessed by forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). However, observational data are susceptible to confounding and reverse causation.

Methods: We selected genetic instruments based on their relevant large-scale genome-wide association studies. Summary statistics of lung function and asthma came from the UK Biobank and SpiroMeta Consortium meta-analysis (n = 400,102). After examining pleiotropy and removing outliers, we applied inverse-variance weighting to estimate the causal association of BMI and BMI-adjusted WHR (WHRadjBMI) with FVC, FEV1, FEV1/FVC, and asthma. Sensitivity analyses were performed using weighted median, MR-Egger, and MRlap methods.

Results: We found that BMI was inversely associated with FVC (effect estimate, -0.167; 95% confidence interval (CI), -0.203 to -0.130) and FEV1 (effect estimate, -0.111; 95%CI, -0.149 to -0.074). Higher BMI was associated with higher FEV1/FVC (effect estimate, 0.079; 95%CI, 0.049 to 0.110) but was not significantly associated with asthma. WHRadjBMI was inversely associated with FVC (effect estimate, -0.132; 95%CI, -0.180 to -0.084) but has no significant association with FEV1. Higher WHR was associated with higher FEV1/FVC (effect estimate, 0.181; 95%CI, 0.130 to 0.232) and with increased risk of asthma (effect estimate, 0.027; 95%CI, 0.001 to 0.053).

Conclusion: We found significant evidence that increased BMI is suggested to be causally related to decreased FVC and FEV1, and increased BMI-adjusted WHR could lead to lower FVC value and higher risk of asthma. Higher BMI and BMI-adjusted WHR were suggested to be causally associated with higher FEV1/FVC.

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Conflict of interest statement

Conflict of Interest Statement:

The authors declare that there is no conflict of interests.

Figures

Figure 1.
Figure 1.
A. Plot of association between BMI and FVC using 80 BMI-associated SNPs. B. Plot of association between BMI and FEV1 using 86 WHR-associated SNPs. C. Plot of association between BMI and FEV1/FVC using 72 WHR-associated SNPs.
Figure 2.
Figure 2.
A. Plot of association between WHRadjBMI and FVC using 28 WHRadjBMI-associated SNPs. B. Plot of association between WHRadjBMI and FEV1 using 31 WHRadjBMI-associated SNPs. C. Plot of association between WHRadjBMI and FEV1/FVC using 28 WHR-associated SNPs.
Figure 3.
Figure 3.
A. Plot of association between BMI and asthma using 94 BMI-associated SNPs. B. Plot of association between WHRadjBMI and asthma using 39 WHRadjBMI-associated SNPs.
See this image and copyright information in PMC

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