Effects of BMI, fat mass, and lean mass on asthma in childhood: a Mendelian randomization study.
<h4>Background</h4>Observational studies have reported associations between body mass index (BMI) and asthma, but confounding and reverse causality remain plausible explanations. We aim to investigate evidence for a causal effect of BMI on asthma using a Mendelian randomization approach....
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Public Library of Science (PLoS)
2014-07-01
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| Series: | PLoS Medicine |
| Online Access: | https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1001669&type=printable |
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| author | Raquel Granell A John Henderson David M Evans George Davey Smith Andrew R Ness Sarah Lewis Tom M Palmer Jonathan A C Sterne |
| author_facet | Raquel Granell A John Henderson David M Evans George Davey Smith Andrew R Ness Sarah Lewis Tom M Palmer Jonathan A C Sterne |
| author_sort | Raquel Granell |
| collection | DOAJ |
| description | <h4>Background</h4>Observational studies have reported associations between body mass index (BMI) and asthma, but confounding and reverse causality remain plausible explanations. We aim to investigate evidence for a causal effect of BMI on asthma using a Mendelian randomization approach.<h4>Methods and findings</h4>We used Mendelian randomization to investigate causal effects of BMI, fat mass, and lean mass on current asthma at age 7½ y in the Avon Longitudinal Study of Parents and Children (ALSPAC). A weighted allele score based on 32 independent BMI-related single nucleotide polymorphisms (SNPs) was derived from external data, and associations with BMI, fat mass, lean mass, and asthma were estimated. We derived instrumental variable (IV) estimates of causal risk ratios (RRs). 4,835 children had available data on BMI-associated SNPs, asthma, and BMI. The weighted allele score was strongly associated with BMI, fat mass, and lean mass (all p-values<0.001) and with childhood asthma (RR 2.56, 95% CI 1.38-4.76 per unit score, p = 0.003). The estimated causal RR for the effect of BMI on asthma was 1.55 (95% CI 1.16-2.07) per kg/m2, p = 0.003. This effect appeared stronger for non-atopic (1.90, 95% CI 1.19-3.03) than for atopic asthma (1.37, 95% CI 0.89-2.11) though there was little evidence of heterogeneity (p = 0.31). The estimated causal RRs for the effects of fat mass and lean mass on asthma were 1.41 (95% CI 1.11-1.79) per 0.5 kg and 2.25 (95% CI 1.23-4.11) per kg, respectively. The possibility of genetic pleiotropy could not be discounted completely; however, additional IV analyses using FTO variant rs1558902 and the other BMI-related SNPs separately provided similar causal effects with wider confidence intervals. Loss of follow-up was unlikely to bias the estimated effects.<h4>Conclusions</h4>Higher BMI increases the risk of asthma in mid-childhood. Higher BMI may have contributed to the increase in asthma risk toward the end of the 20th century. Please see later in the article for the Editors' Summary. |
| format | Article |
| id | doaj-art-e2e98d1ae8d241e6b4adcdb017537512 |
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| issn | 1549-1277 1549-1676 |
| language | English |
| publishDate | 2014-07-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj-art-e2e98d1ae8d241e6b4adcdb0175375122025-08-20T02:22:20ZengPublic Library of Science (PLoS)PLoS Medicine1549-12771549-16762014-07-01117e100166910.1371/journal.pmed.1001669Effects of BMI, fat mass, and lean mass on asthma in childhood: a Mendelian randomization study.Raquel GranellA John HendersonDavid M EvansGeorge Davey SmithAndrew R NessSarah LewisTom M PalmerJonathan A C Sterne<h4>Background</h4>Observational studies have reported associations between body mass index (BMI) and asthma, but confounding and reverse causality remain plausible explanations. We aim to investigate evidence for a causal effect of BMI on asthma using a Mendelian randomization approach.<h4>Methods and findings</h4>We used Mendelian randomization to investigate causal effects of BMI, fat mass, and lean mass on current asthma at age 7½ y in the Avon Longitudinal Study of Parents and Children (ALSPAC). A weighted allele score based on 32 independent BMI-related single nucleotide polymorphisms (SNPs) was derived from external data, and associations with BMI, fat mass, lean mass, and asthma were estimated. We derived instrumental variable (IV) estimates of causal risk ratios (RRs). 4,835 children had available data on BMI-associated SNPs, asthma, and BMI. The weighted allele score was strongly associated with BMI, fat mass, and lean mass (all p-values<0.001) and with childhood asthma (RR 2.56, 95% CI 1.38-4.76 per unit score, p = 0.003). The estimated causal RR for the effect of BMI on asthma was 1.55 (95% CI 1.16-2.07) per kg/m2, p = 0.003. This effect appeared stronger for non-atopic (1.90, 95% CI 1.19-3.03) than for atopic asthma (1.37, 95% CI 0.89-2.11) though there was little evidence of heterogeneity (p = 0.31). The estimated causal RRs for the effects of fat mass and lean mass on asthma were 1.41 (95% CI 1.11-1.79) per 0.5 kg and 2.25 (95% CI 1.23-4.11) per kg, respectively. The possibility of genetic pleiotropy could not be discounted completely; however, additional IV analyses using FTO variant rs1558902 and the other BMI-related SNPs separately provided similar causal effects with wider confidence intervals. Loss of follow-up was unlikely to bias the estimated effects.<h4>Conclusions</h4>Higher BMI increases the risk of asthma in mid-childhood. Higher BMI may have contributed to the increase in asthma risk toward the end of the 20th century. Please see later in the article for the Editors' Summary.https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1001669&type=printable |
| spellingShingle | Raquel Granell A John Henderson David M Evans George Davey Smith Andrew R Ness Sarah Lewis Tom M Palmer Jonathan A C Sterne Effects of BMI, fat mass, and lean mass on asthma in childhood: a Mendelian randomization study. PLoS Medicine |
| title | Effects of BMI, fat mass, and lean mass on asthma in childhood: a Mendelian randomization study. |
| title_full | Effects of BMI, fat mass, and lean mass on asthma in childhood: a Mendelian randomization study. |
| title_fullStr | Effects of BMI, fat mass, and lean mass on asthma in childhood: a Mendelian randomization study. |
| title_full_unstemmed | Effects of BMI, fat mass, and lean mass on asthma in childhood: a Mendelian randomization study. |
| title_short | Effects of BMI, fat mass, and lean mass on asthma in childhood: a Mendelian randomization study. |
| title_sort | effects of bmi fat mass and lean mass on asthma in childhood a mendelian randomization study |
| url | https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1001669&type=printable |
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