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.
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/m(2), 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.
Department of Internal Medicine, Section of Respiratory Medicine, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark Department of Public Health, Section of Social Medicine, University of Copenhagen, Copenhagen, Denmark The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Yunus
Y
Çolak
The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
Shoaib
S
Afzal
Department of Public Health, Section of Social Medicine, University of Copenhagen, Copenhagen, Denmark The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark Medical Unit, Respiratory Section, Hvidovre Hospital, Copenhagen University Hospital, Hvidovre, Denmark.
Peter
P
Lange
The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
Børge G
BG
Nordestgaard
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001249:Asthma / Q000150:complications* / Q000453:epidemiology / Q000503:physiopathology; D015992:Body Mass Index; D003718:Denmark / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015994:Incidence; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009765:Obesity / Q000150:complications* / Q000453:epidemiology / Q000235:genetics; D019370:Observation / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D011159:Population Surveillance / Q000379:methods*; D012135:Respiratory Sounds / Q000209:etiology / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D055815:Young Adult
D008565:Membrane Proteins
Asthma; Asthma Epidemiology; Asthma Genetics; Clinical Epidemiology