Estimating the causal effect of body mass index on hay fever, asthma and lung function using Mendelian randomization

T Skaaby; A E Taylor; B H Thuesen; R K Jacobsen; N Friedrich; L T Møllehave; S Hansen; S C Larsen; U Völker; M Nauck; H Völzke; T. Hansen; O. Pedersen; T. Jørgensen; L Paternoster; M Munafò; N. Grarup; A. Linneberg

doi:10.1111/all.13242

Estimating the causal effect of body mass index on hay fever, asthma and lung function using Mendelian randomization

T Skaaby, A E Taylor, B H Thuesen, R K Jacobsen, N Friedrich, L T Møllehave, S Hansen, S C Larsen, U Völker, M Nauck, H Völzke, T. Hansen, O. Pedersen, T. Jørgensen, L Paternoster, M Munafò, N. Grarup, A. Linneberg

22 Citations (Scopus)

Abstract

BACKGROUND: Observational studies have shown that body mass index (BMI) is positively associated with asthma. However, observational data are prone to confounding and reverse causation. In Mendelian randomization, genetic variants are used as unconfounded markers of exposures to examine causal effects. We examined the causal effect of BMI on asthma, hay fever, allergic sensitization, serum total immunoglobulin E (IgE), forced expiratory volume in one-second (FEV1) and forced vital capacity (FVC).

METHODS: We included 490 497 participants in the observational and 162 124 participants in the genetic analyses. A genetic risk score (GRS) was created using 26 BMI-associated single nucleotide polymorphisms (SNPs). Results were pooled in meta-analyses and expressed as odds ratios (ORs) or β-estimates with 95% confidence interval (CI).

RESULTS: The GRS was significantly associated with asthma (OR=1.009; 95% CI: 1.004, 1.013), but not with hay fever (OR= 0.998; 95% CI: 0.994, 1.002) or allergic sensitization (OR=0.999; 95% CI: 0.986, 1.012) per BMI-increasing allele. The GRS was significantly associated with decrease in FEV1: β=-0.0012 (95% CI: -0.0019, -0.0006) and FVC: β=-0.0022 (95% CI: -0.0031, -0.0014) per BMI-increasing allele. Effect sizes estimated by instrumental variable analyses were OR=1.07 (95% CI: 1.03, 1.10) for asthma, a 9 ml decrease in FEV1 (95% CI: 2.0-15 mL decrease) and a 16 ml decrease in FVC (95% CI: 7.0-24 mL decrease) per 1 kg/m2higher BMI.

CONCLUSIONS: The results support the conclusion that increasing BMI is causally related to higher prevalence of asthma and decreased lung function, but not with hay fever or biomarkers of allergy.

Original language	English
Journal	Allergy
Volume	73
Issue number	1
Pages (from-to)	153-164
Number of pages	12
ISSN	0105-4538
DOIs	https://doi.org/10.1111/all.13242
Publication status	Published - 2018

Keywords

Journal Article
allergic sensitization
asthma
allergic disease
hay fever
serum-specific IgE

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10.1111/all.13242

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Skaaby, T., Taylor, A. E., Thuesen, B. H., Jacobsen, R. K., Friedrich, N., Møllehave, L. T., Hansen, S., Larsen, S. C., Völker, U., Nauck, M., Völzke, H., Hansen, T., Pedersen, O., Jørgensen, T., Paternoster, L., Munafò, M., Grarup, N., & Linneberg, A. (2018). Estimating the causal effect of body mass index on hay fever, asthma and lung function using Mendelian randomization. Allergy, 73(1), 153-164. https://doi.org/10.1111/all.13242

Skaaby, T, Taylor, AE, Thuesen, BH, Jacobsen, RK, Friedrich, N, Møllehave, LT, Hansen, S, Larsen, SC, Völker, U, Nauck, M, Völzke, H, Hansen, T , Pedersen, O, Jørgensen, T, Paternoster, L, Munafò, M, Grarup, N & Linneberg, A 2018, 'Estimating the causal effect of body mass index on hay fever, asthma and lung function using Mendelian randomization', Allergy, vol. 73, no. 1, pp. 153-164. https://doi.org/10.1111/all.13242

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title = "Estimating the causal effect of body mass index on hay fever, asthma and lung function using Mendelian randomization",

abstract = "BACKGROUND: Observational studies have shown that body mass index (BMI) is positively associated with asthma. However, observational data are prone to confounding and reverse causation. In Mendelian randomization, genetic variants are used as unconfounded markers of exposures to examine causal effects. We examined the causal effect of BMI on asthma, hay fever, allergic sensitization, serum total immunoglobulin E (IgE), forced expiratory volume in one-second (FEV1) and forced vital capacity (FVC).METHODS: We included 490 497 participants in the observational and 162 124 participants in the genetic analyses. A genetic risk score (GRS) was created using 26 BMI-associated single nucleotide polymorphisms (SNPs). Results were pooled in meta-analyses and expressed as odds ratios (ORs) or β-estimates with 95% confidence interval (CI).RESULTS: The GRS was significantly associated with asthma (OR=1.009; 95% CI: 1.004, 1.013), but not with hay fever (OR= 0.998; 95% CI: 0.994, 1.002) or allergic sensitization (OR=0.999; 95% CI: 0.986, 1.012) per BMI-increasing allele. The GRS was significantly associated with decrease in FEV1: β=-0.0012 (95% CI: -0.0019, -0.0006) and FVC: β=-0.0022 (95% CI: -0.0031, -0.0014) per BMI-increasing allele. Effect sizes estimated by instrumental variable analyses were OR=1.07 (95% CI: 1.03, 1.10) for asthma, a 9 ml decrease in FEV1 (95% CI: 2.0-15 mL decrease) and a 16 ml decrease in FVC (95% CI: 7.0-24 mL decrease) per 1 kg/m2higher BMI.CONCLUSIONS: The results support the conclusion that increasing BMI is causally related to higher prevalence of asthma and decreased lung function, but not with hay fever or biomarkers of allergy.",

keywords = "Journal Article, allergic sensitization, asthma, allergic disease, hay fever, serum-specific IgE",

author = "T Skaaby and Taylor, {A E} and Thuesen, {B H} and Jacobsen, {R K} and N Friedrich and M{\o}llehave, {L T} and S Hansen and Larsen, {S C} and U V{\"o}lker and M Nauck and H V{\"o}lzke and T. Hansen and O. Pedersen and T. J{\o}rgensen and L Paternoster and M Munaf{\`o} and N. Grarup and A. Linneberg",

note = "{\textcopyright} 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.",

year = "2018",

doi = "10.1111/all.13242",

language = "English",

volume = "73",

pages = "153--164",

journal = "Allergy: European Journal of Allergy and Clinical Immunology",

issn = "0105-4538",

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TY - JOUR

T1 - Estimating the causal effect of body mass index on hay fever, asthma and lung function using Mendelian randomization

AU - Skaaby, T

AU - Taylor, A E

AU - Thuesen, B H

AU - Jacobsen, R K

AU - Friedrich, N

AU - Møllehave, L T

AU - Hansen, S

AU - Larsen, S C

AU - Völker, U

AU - Nauck, M

AU - Völzke, H

AU - Hansen, T.

AU - Pedersen, O.

AU - Jørgensen, T.

AU - Paternoster, L

AU - Munafò, M

AU - Grarup, N.

AU - Linneberg, A.

PY - 2018

Y1 - 2018

N2 - BACKGROUND: Observational studies have shown that body mass index (BMI) is positively associated with asthma. However, observational data are prone to confounding and reverse causation. In Mendelian randomization, genetic variants are used as unconfounded markers of exposures to examine causal effects. We examined the causal effect of BMI on asthma, hay fever, allergic sensitization, serum total immunoglobulin E (IgE), forced expiratory volume in one-second (FEV1) and forced vital capacity (FVC).METHODS: We included 490 497 participants in the observational and 162 124 participants in the genetic analyses. A genetic risk score (GRS) was created using 26 BMI-associated single nucleotide polymorphisms (SNPs). Results were pooled in meta-analyses and expressed as odds ratios (ORs) or β-estimates with 95% confidence interval (CI).RESULTS: The GRS was significantly associated with asthma (OR=1.009; 95% CI: 1.004, 1.013), but not with hay fever (OR= 0.998; 95% CI: 0.994, 1.002) or allergic sensitization (OR=0.999; 95% CI: 0.986, 1.012) per BMI-increasing allele. The GRS was significantly associated with decrease in FEV1: β=-0.0012 (95% CI: -0.0019, -0.0006) and FVC: β=-0.0022 (95% CI: -0.0031, -0.0014) per BMI-increasing allele. Effect sizes estimated by instrumental variable analyses were OR=1.07 (95% CI: 1.03, 1.10) for asthma, a 9 ml decrease in FEV1 (95% CI: 2.0-15 mL decrease) and a 16 ml decrease in FVC (95% CI: 7.0-24 mL decrease) per 1 kg/m2higher BMI.CONCLUSIONS: The results support the conclusion that increasing BMI is causally related to higher prevalence of asthma and decreased lung function, but not with hay fever or biomarkers of allergy.

AB - BACKGROUND: Observational studies have shown that body mass index (BMI) is positively associated with asthma. However, observational data are prone to confounding and reverse causation. In Mendelian randomization, genetic variants are used as unconfounded markers of exposures to examine causal effects. We examined the causal effect of BMI on asthma, hay fever, allergic sensitization, serum total immunoglobulin E (IgE), forced expiratory volume in one-second (FEV1) and forced vital capacity (FVC).METHODS: We included 490 497 participants in the observational and 162 124 participants in the genetic analyses. A genetic risk score (GRS) was created using 26 BMI-associated single nucleotide polymorphisms (SNPs). Results were pooled in meta-analyses and expressed as odds ratios (ORs) or β-estimates with 95% confidence interval (CI).RESULTS: The GRS was significantly associated with asthma (OR=1.009; 95% CI: 1.004, 1.013), but not with hay fever (OR= 0.998; 95% CI: 0.994, 1.002) or allergic sensitization (OR=0.999; 95% CI: 0.986, 1.012) per BMI-increasing allele. The GRS was significantly associated with decrease in FEV1: β=-0.0012 (95% CI: -0.0019, -0.0006) and FVC: β=-0.0022 (95% CI: -0.0031, -0.0014) per BMI-increasing allele. Effect sizes estimated by instrumental variable analyses were OR=1.07 (95% CI: 1.03, 1.10) for asthma, a 9 ml decrease in FEV1 (95% CI: 2.0-15 mL decrease) and a 16 ml decrease in FVC (95% CI: 7.0-24 mL decrease) per 1 kg/m2higher BMI.CONCLUSIONS: The results support the conclusion that increasing BMI is causally related to higher prevalence of asthma and decreased lung function, but not with hay fever or biomarkers of allergy.

KW - Journal Article

KW - allergic sensitization

KW - asthma

KW - allergic disease

KW - hay fever

KW - serum-specific IgE

U2 - 10.1111/all.13242

DO - 10.1111/all.13242

M3 - Journal article

C2 - 28675761

SN - 0105-4538

VL - 73

SP - 153

EP - 164

JO - Allergy: European Journal of Allergy and Clinical Immunology

JF - Allergy: European Journal of Allergy and Clinical Immunology

IS - 1

ER -

Estimating the causal effect of body mass index on hay fever, asthma and lung function using Mendelian randomization

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