Effects of BMI, fat mass, and lean mass on asthma in childhood: a Mendelian randomization study.

<h4>Background</h4>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....

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Autores principales:	Raquel Granell, A John Henderson, David M Evans, George Davey Smith, Andrew R Ness, Sarah Lewis, Tom M Palmer, Jonathan A C Sterne
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R
Acceso en línea:	https://doaj.org/article/e2e98d1ae8d241e6b4adcdb017537512
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spelling	oai:doaj.org-article:e2e98d1ae8d241e6b4adcdb0175375122021-11-25T05:36:43ZEffects of BMI, fat mass, and lean mass on asthma in childhood: a Mendelian randomization study.1549-12771549-167610.1371/journal.pmed.1001669https://doaj.org/article/e2e98d1ae8d241e6b4adcdb0175375122014-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24983943/?tool=EBIhttps://doaj.org/toc/1549-1277https://doaj.org/toc/1549-1676<h4>Background</h4>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.<h4>Methods and findings</h4>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.<h4>Conclusions</h4>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. Please see later in the article for the Editors' Summary.Raquel GranellA John HendersonDavid M EvansGeorge Davey SmithAndrew R NessSarah LewisTom M PalmerJonathan A C SternePublic Library of Science (PLoS)articleMedicineRENPLoS Medicine, Vol 11, Iss 7, p e1001669 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R
spellingShingle	Medicine R Raquel Granell A John Henderson David M Evans George Davey Smith Andrew R Ness Sarah Lewis Tom M Palmer Jonathan A C Sterne Effects of BMI, fat mass, and lean mass on asthma in childhood: a Mendelian randomization study.
description	<h4>Background</h4>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.<h4>Methods and findings</h4>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.<h4>Conclusions</h4>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. Please see later in the article for the Editors' Summary.
format	article
author	Raquel Granell A John Henderson David M Evans George Davey Smith Andrew R Ness Sarah Lewis Tom M Palmer Jonathan A C Sterne
author_facet	Raquel Granell A John Henderson David M Evans George Davey Smith Andrew R Ness Sarah Lewis Tom M Palmer Jonathan A C Sterne
author_sort	Raquel Granell
title	Effects of BMI, fat mass, and lean mass on asthma in childhood: a Mendelian randomization study.
title_short	Effects of BMI, fat mass, and lean mass on asthma in childhood: a Mendelian randomization study.
title_full	Effects of BMI, fat mass, and lean mass on asthma in childhood: a Mendelian randomization study.
title_fullStr	Effects of BMI, fat mass, and lean mass on asthma in childhood: a Mendelian randomization study.
title_full_unstemmed	Effects of BMI, fat mass, and lean mass on asthma in childhood: a Mendelian randomization study.
title_sort	effects of bmi, fat mass, and lean mass on asthma in childhood: a mendelian randomization study.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/e2e98d1ae8d241e6b4adcdb017537512
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Effects of BMI, fat mass, and lean mass on asthma in childhood: a Mendelian randomization study.

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