TY - JOUR
T1 - Estimating the causal effect of body mass index on hay fever, asthma, and lung function using Mendelian randomization
AU - Skaaby, Tea
AU - Taylor, Amy E
AU - Thuesen, Betina Heinsbaek
AU - Jacobsen, Rikke K.
AU - Friedrich, Nele
AU - Møllehave, Line Tang
AU - Hansen, Susanne
AU - Larsen, Sofus C
AU - Völker, Uwe
AU - Nauck, Matthias
AU - Völzke, Henry
AU - Hansen, Torben
AU - Pedersen, Oluf
AU - Jørgensen, Torben
AU - Paternoster, Lavinia
AU - R Munafò, Marcus
AU - Grarup, Niels
AU - Linneberg, Allan
N1 - © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.
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/m
2 higher 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/m
2 higher 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
KW - Body Mass Index
KW - Genetic Predisposition to Disease
KW - Humans
KW - Middle Aged
KW - Genotype
KW - Male
KW - Forced Expiratory Volume
KW - Immunoglobulin E/immunology
KW - Rhinitis, Allergic, Seasonal/epidemiology
KW - Alleles
KW - Adult
KW - Female
KW - Polymorphism, Single Nucleotide
KW - Respiratory Function Tests
KW - Asthma/epidemiology
KW - Odds Ratio
UR - http://www.scopus.com/inward/record.url?scp=85026666040&partnerID=8YFLogxK
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 -