Effects of BMI, Fat Mass, and Lean Mass on Asthma in Childhood: A Mendelian Randomization Study

Raquel Granell; A J W Henderson; David Evans; George Davey Smith; Andy R Ness; Sarah P Lewis; Tom M. Palmer; Jonathan A C Sterne

doi:10.1371/journal.pmed.1001669

Effects of BMI, Fat Mass, and Lean Mass on Asthma in Childhood: A Mendelian Randomization Study

Raquel Granell^*, A J W Henderson, David Evans, George Davey Smith, Andy R Ness, Sarah P Lewis, Tom M. Palmer, Jonathan A C Sterne

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

55 Citations (Scopus)

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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.

Original language	English
Article number	e1001669
Number of pages	14
Journal	PLoS Medicine
Volume	11
Issue number	7
DOIs	https://doi.org/10.1371/journal.pmed.1001669
Publication status	Published - 1 Jul 2014

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2 Finished

MRC UoB UNITE Unit - Programme 1
Davey Smith, G.
1/06/13 → 31/03/18
Project: Research
EXTENSION OF RD1321 VIA IOP.
Golding, J.
1/02/01 → 1/02/06
Project: Research

Dr Raquel Granell
- Raquel.Granell@bristol.ac.uk
- Bristol Medical School (PHS) - Senior Research Fellow
- Bristol Population Health Science Institute
Person: Academic , Member
Professor Jonathan A C Sterne
- Jonathan.Sterne@bristol.ac.uk
- Bristol Medical School (PHS) - Professor of Medical Statistics and Epidemiology
- Bristol Population Health Science Institute
- NIHR Applied Research Collaboration West (NIHR ARC West)
- Infection and Immunity
Person: Academic , Member

Cite this

@article{8ff06423a80b49c9a15cc4ca5b0a07cd,

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.",

author = "Raquel Granell and Henderson, {A J W} and David Evans and {Davey Smith}, George and Ness, {Andy R} and Lewis, {Sarah P} 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",

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Effects of BMI, Fat Mass, and Lean Mass on Asthma in Childhood : A Mendelian Randomization Study. / Granell, Raquel; Henderson, A J W; Evans, David; Davey Smith, George ; Ness, Andy R; Lewis, Sarah P; Palmer, Tom M.; Sterne, Jonathan A C.

In: PLoS Medicine, Vol. 11, No. 7, e1001669, 01.07.2014.

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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 J W

AU - Evans, David

AU - Davey Smith, George

AU - Ness, Andy R

AU - Lewis, Sarah P

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.

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.

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DO - 10.1371/journal.pmed.1001669

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Effects of BMI, Fat Mass, and Lean Mass on Asthma in Childhood: A Mendelian Randomization Study

Abstract

Access to Document

MRC UoB UNITE Unit - Programme 1

EXTENSION OF RD1321 VIA IOP.

Dr Raquel Granell

Professor Jonathan A C Sterne

Cite this