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

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Effects of BMI, fat mass, and lean mass on asthma in childhood: a Mendelian randomization study. / Granell, Raquel; Henderson, A. John; Evans, David M. et al.
In: PLoS Medicine, Vol. 11, No. 7, e1001669, 01.07.2014.

Research output: Contribution to Journal/MagazineJournal articlepeer-review

Harvard

Granell, R, Henderson, AJ, Evans, DM, Smith, GD, Ness, AR, Lewis, S, Palmer, TM & Sterne, JAC 2014, 'Effects of BMI, fat mass, and lean mass on asthma in childhood: a Mendelian randomization study', PLoS Medicine, vol. 11, no. 7, e1001669. https://doi.org/10.1371/journal.pmed.1001669

APA

Granell, R., Henderson, A. J., Evans, D. M., Smith, G. D., Ness, A. R., Lewis, S., Palmer, T. M., & Sterne, J. A. C. (2014). Effects of BMI, fat mass, and lean mass on asthma in childhood: a Mendelian randomization study. PLoS Medicine, 11(7), Article e1001669. https://doi.org/10.1371/journal.pmed.1001669

Vancouver

Granell R, Henderson AJ, Evans DM, Smith GD, Ness AR, Lewis S et al. Effects of BMI, fat mass, and lean mass on asthma in childhood: a Mendelian randomization study. PLoS Medicine. 2014 Jul 1;11(7):e1001669. doi: 10.1371/journal.pmed.1001669

Author

Granell, Raquel ; Henderson, A. John ; Evans, David M. et al. / Effects of BMI, fat mass, and lean mass on asthma in childhood : a Mendelian randomization study. In: PLoS Medicine. 2014 ; Vol. 11, No. 7.

Bibtex

@article{32b2dacf9e5e438f803c3b5bba21e4f5,
title = "Effects of BMI, fat mass, and lean mass on asthma in childhood: a Mendelian randomization study",
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. Please see later in the article for the Editors' Summary.",
author = "Raquel Granell and Henderson, {A. John} and Evans, {David M.} and Smith, {George Davey} and Ness, {Andrew R.} and Sarah Lewis and Palmer, {Tom M.} and Sterne, {Jonathan A. C.}",
year = "2014",
month = jul,
day = "1",
doi = "10.1371/journal.pmed.1001669",
language = "English",
volume = "11",
journal = "PLoS Medicine",
issn = "1549-1277",
publisher = "Public Library of Science",
number = "7",

}

RIS

TY - JOUR

T1 - Effects of BMI, fat mass, and lean mass on asthma in childhood

T2 - a Mendelian randomization study

AU - Granell, Raquel

AU - Henderson, A. John

AU - Evans, David M.

AU - Smith, George Davey

AU - Ness, Andrew R.

AU - Lewis, Sarah

AU - Palmer, Tom M.

AU - Sterne, Jonathan A. C.

PY - 2014/7/1

Y1 - 2014/7/1

N2 - 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. Please see later in the article for the Editors' Summary.

AB - 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. Please see later in the article for the Editors' Summary.

U2 - 10.1371/journal.pmed.1001669

DO - 10.1371/journal.pmed.1001669

M3 - Journal article

C2 - 24983943

VL - 11

JO - PLoS Medicine

JF - PLoS Medicine

SN - 1549-1277

IS - 7

M1 - e1001669

ER -