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Obese individuals experience wheezing without asthma but not asthma without wheezing: a Mendelian randomisation study of 85 437 adults from the Copenhagen General Population Study
  1. Yunus Çolak1,2,3,4,
  2. Shoaib Afzal3,4,5,
  3. Peter Lange2,3,4,5,6,
  4. Børge G Nordestgaard3,4,5
  1. 1Department of Internal Medicine, Section of Respiratory Medicine, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
  2. 2Department of Public Health, Section of Social Medicine, University of Copenhagen, Copenhagen, Denmark
  3. 3The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
  4. 4Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  5. 5Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
  6. 6Medical Unit, Respiratory Section, Hvidovre Hospital, Copenhagen University Hospital, Hvidovre, Denmark
  1. Correspondence to Professor Børge G Nordestgaard, Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev Ringvej 75, Herlev DK-2730, Denmark; Boerge.Nordestgaard{at}regionh.dk

Abstract

Background Observational studies suggest that obesity is associated with increased risk of asthma. However, it is unknown whether this could be explained by wheezing. We tested the hypothesis that high body mass index (BMI) observationally and genetically is associated with high risk of wheezing and asthma, and that the association between high BMI and asthma is explained by wheezing.

Methods We genotyped 85 437 individuals aged 20–100 years from the Copenhagen General Population Study for FTO (rs9939609), MC4R (rs17782313), TMEM18 (rs6548238) GNPDA2 (rs10938397) and BDNF (rs10767664); 14 500 individuals experienced wheezing and 5406 had asthma. Wheezing was self-reported, and asthma was ascertained through self-report, hospital contacts with asthma, and/or receiving medication for asthma. BMI was calculated as measured weight divided by measured height squared (kg/m2).

Results In observational analyses versus BMI of 18.5–22.4 kg/m2, ORs for wheezing were 1.23 (95% CI 1.00 to 1.52) for BMI <18.5 kg/m2, 1.17 (1.10 to 1.25) for 22.5–24.9 kg/m2, 1.44 (1.35 to 1.54) for 25–27.4 kg/m2, 1.86 (1.73 to 1.99) for 27.5–29.9 kg/m2, 2.48 (2.31 to 2.66) for 30–34.9 kg/m2, 3.86 (3.48 to 4.28) for 35–39.9 kg/m2 and 6.05 (5.12 to 7.14) for BMI ≥40 kg/m2. Corresponding ORs for asthma were 1.28 (0.95 to 1.74), 1.07 (0.97 to 1.17), 1.14 (1.04 to 1.25), 1.32 (1.20 to 1.46), 1.39 (1.25 to 1.54), 1.54 (1.31 to 1.81) and 1.99 (1.55 to 2.56), respectively. Compared with BMI allele score 0–4, scores 5, 6 and 7–10 were associated with 0.22, 0.51 and 0.76 kg/m2 higher BMI, respectively. Genetically determined ORs per unit higher BMI were 1.22 (1.15 to 1.31) for wheezing, 1.18 (1.10 to 1.27) for wheezing without asthma, 1.08 (0.98 to 1.19) for asthma, and 0.85 (0.73 to 0.99) for asthma without wheezing. Corresponding observational ORs were 1.09 (1.09 to 1.10), 1.09 (1.08 to 1.09), 1.03 (1.03 to 1.04) and 0.99 (0.98 to 1.00), respectively.

Conclusions High BMI was associated with high risk of wheezing without asthma, but not with high risk of asthma without wheezing.

  • Asthma
  • Asthma Genetics
  • Asthma Epidemiology
  • Clinical Epidemiology

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