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Effects of BMI, fat mass, and lean mass on asthma in childhood : a Mendelian Randomization Study
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Granell, Raquel, Henderson, A. John, Evans, David M., Smith, George Davey, Ness, Andrew R., Lewis, Sarah, Palmer, Tom M. and Sterne, Jonathan A. C. (2014) Effects of BMI, fat mass, and lean mass on asthma in childhood : a Mendelian Randomization Study. PLoS Medicine, Volume 11 (Number 7). Article number e1001669. doi:10.1371/journal.pmed.1001669 ISSN 1549-1277.
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Official URL: http://dx.doi.org/10.1371/journal.pmed.1001669
Abstract
Background
Observational studies have reported associations between body mass index (BMI) and asthma, but confounding and reverse causality remain plausible explanations. We aim to investigate evidence for a causal effect of BMI on asthma using a Mendelian randomization approach.
Methods and Findings
We used Mendelian randomization to investigate causal effects of BMI, fat mass, and lean mass on current asthma at age 7½ y in the Avon Longitudinal Study of Parents and Children (ALSPAC). A weighted allele score based on 32 independent BMI-related single nucleotide polymorphisms (SNPs) was derived from external data, and associations with BMI, fat mass, lean mass, and asthma were estimated. We derived instrumental variable (IV) estimates of causal risk ratios (RRs). 4,835 children had available data on BMI-associated SNPs, asthma, and BMI. The weighted allele score was strongly associated with BMI, fat mass, and lean mass (all p-values<0.001) and with childhood asthma (RR 2.56, 95% CI 1.38–4.76 per unit score, p = 0.003). The estimated causal RR for the effect of BMI on asthma was 1.55 (95% CI 1.16–2.07) per kg/m2, p = 0.003. This effect appeared stronger for non-atopic (1.90, 95% CI 1.19–3.03) than for atopic asthma (1.37, 95% CI 0.89–2.11) though there was little evidence of heterogeneity (p = 0.31). The estimated causal RRs for the effects of fat mass and lean mass on asthma were 1.41 (95% CI 1.11–1.79) per 0.5 kg and 2.25 (95% CI 1.23–4.11) per kg, respectively. The possibility of genetic pleiotropy could not be discounted completely; however, additional IV analyses using FTO variant rs1558902 and the other BMI-related SNPs separately provided similar causal effects with wider confidence intervals. Loss of follow-up was unlikely to bias the estimated effects.
Conclusions
Higher BMI increases the risk of asthma in mid-childhood. Higher BMI may have contributed to the increase in asthma risk toward the end of the 20th century.
Item Type: | Journal Article | ||||||||
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Subjects: | Q Science > QP Physiology R Medicine > RA Public aspects of medicine > RA0421 Public health. Hygiene. Preventive Medicine R Medicine > RC Internal medicine R Medicine > RJ Pediatrics > RJ101 Child Health. Child health services |
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Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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Library of Congress Subject Headings (LCSH): | Body mass index, Human body -- Composition, Asthma, Asthma in children | ||||||||
Journal or Publication Title: | PLoS Medicine | ||||||||
Publisher: | Public Library of Science | ||||||||
ISSN: | 1549-1277 | ||||||||
Official Date: | 1 July 2014 | ||||||||
Dates: |
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Volume: | Volume 11 | ||||||||
Number: | Number 7 | ||||||||
Article Number: | Article number e1001669 | ||||||||
DOI: | 10.1371/journal.pmed.1001669 | ||||||||
Status: | Peer Reviewed | ||||||||
Publication Status: | Published | ||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||
Date of first compliant deposit: | 27 December 2015 | ||||||||
Date of first compliant Open Access: | 27 December 2015 | ||||||||
Funder: | Medical Research Council (Great Britain) (MRC), Wellcome Trust (London, England), University of Bristol | ||||||||
Grant number: | 092731 (Wellcome Trust), 0401540 (MRC), |
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