TY - JOUR

T1 - Obese individuals experience wheezing without asthma but not asthma without wheezing

T2 - a Mendelian randomisation study of 85 437 adults from the Copenhagen General Population Study

AU - Çolak, Yunus

AU - Afzal, Shoaib

AU - Lange, Peter

AU - Nordestgaard, Børge G

N1 - Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

PY - 2016

Y1 - 2016

N2 - 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/m(2)).RESULTS: In observational analyses versus BMI of 18.5-22.4 kg/m(2), ORs for wheezing were 1.23 (95% CI 1.00 to 1.52) for BMI <18.5 kg/m(2), 1.17 (1.10 to 1.25) for 22.5-24.9 kg/m(2), 1.44 (1.35 to 1.54) for 25-27.4 kg/m(2), 1.86 (1.73 to 1.99) for 27.5-29.9 kg/m(2), 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/m(2) and 6.05 (5.12 to 7.14) for BMI ≥40 kg/m(2). 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/m(2) 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.

AB - 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/m(2)).RESULTS: In observational analyses versus BMI of 18.5-22.4 kg/m(2), ORs for wheezing were 1.23 (95% CI 1.00 to 1.52) for BMI <18.5 kg/m(2), 1.17 (1.10 to 1.25) for 22.5-24.9 kg/m(2), 1.44 (1.35 to 1.54) for 25-27.4 kg/m(2), 1.86 (1.73 to 1.99) for 27.5-29.9 kg/m(2), 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/m(2) and 6.05 (5.12 to 7.14) for BMI ≥40 kg/m(2). 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/m(2) 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.

U2 - 10.1136/thoraxjnl-2015-207379

DO - 10.1136/thoraxjnl-2015-207379

M3 - Journal article

C2 - 26504195

VL - 71

SP - 247

EP - 254

JO - Thorax

JF - Thorax

SN - 0040-6376

ER -