A life course approach to elucidate the role of adiposity in asthma risk: evidence from a Mendelian randomisation study

Abstract

BackgroundAdiposity is associated with asthma although studies do not usually explore the inter-related role of childhood and adult adiposity in asthma risk using a life course perspective.MethodsWe conducted a Mendelian randomisation (MR) study using genetic instruments for childhood body mass index (BMI) (n=47 541), childhood obesity (n=29 822) and adult BMI (n=681 725) applied to the UK Biobank (n=401 837), with validation in a genome-wide association study of asthma (GABRIEL, n=5616). We used inverse variance weighting and other sensitivity analyses to examine the relationship between adiposity and asthma risk. We assessed mediation using multivariable Mendelian randomisation (MVMR) analysis.ResultsChildhood BMI was related to asthma in the UK Biobank (OR 1.10 per SD increase, 95% CI 0.99 to 1.22). Adult BMI was associated with asthma risk (OR 1.33 per SD increase, 95% CI 1.25 to 1.43). Analyses in GABRIEL gave directionally consistent results but with wide CI. The relationship between childhood obesity and asthma risk was less clear in both data sources. MVMR suggested the relation of childhood BMI with asthma risk was largely mediated via adult BMI.ConclusionAdiposity in childhood likely cause asthma, but the effect is primarily mediated via adult BMI.

Association Between Environmental Factors and Asthma Using Mendelian Randomization: Increased Effect of Body Mass Index on Adult-Onset Moderate-to-Severe Asthma Subtypes

“…The estimates of childhood BMI in total asthma showed significant effects by IVW (OR/CI95 = 1.11/1.03-1.19, P -value = 3.43E–03) and GSMR (OR/CI95 = 1.12/1.04–1.20, P -value = 3.43E-03) but not by the weighted median method (OR/CI95 = 1.09/0.99–1.21, P -value = 0.07). However, no significant causal effect was found between childhood BMI and the 4 asthma subtypes by IVW, GSMR, and weighted median, consistent with the previous report ( Au Yeung et al, 2021 ). Based on the previous study ( Au Yeung et al, 2021 ) and our result, childhood BMI has a weak causal impact on asthma but not on any specific subtype.…”

“…However, no significant causal effect was found between childhood BMI and the 4 asthma subtypes by IVW, GSMR, and weighted median, consistent with the previous report ( Au Yeung et al, 2021 ). Based on the previous study ( Au Yeung et al, 2021 ) and our result, childhood BMI has a weak causal impact on asthma but not on any specific subtype.…”

“…Our two-sample MR using 25 childhood BMI SNPs ( Vogelezang et al, 2020 ) supports a causal relationship with asthma. However, based on the previous study ( Au Yeung et al, 2021 ) and our result, childhood BMI has a weak causal impact on asthma but not on any specific subtype.…”

“…Notably, a recent study that used the IVW method confirmed the causal impact of adult BMI on asthma, whereas the possible impact of childhood BMI on the risk of asthma was less clear, mediated predominantly by its relationship with adult BMI, implicating that children with high BMI can reduce their risk of asthma by becoming normal-weight adults. This study was limited, in that there were far fewer childhood BMI SNPs ( N = 14 and 5) than adult BMI SNPs ( N = 323 and 115), decreasing the power of the MR estimation ( Au Yeung et al, 2021 ). Our two-sample MR using 25 childhood BMI SNPs ( Vogelezang et al, 2020 ) supports a causal relationship with asthma.…”

Evaluating the Causal Association Between Educational Attainment and Asthma Using a Mendelian Randomization Design

“…Importantly, these GWAS datasets are publicly available and promote additional analyses, such as MR analysis, to evaluate the causal association between common risk factors and asthma. These risk factors include soluble interleukin-6 receptor level ( Rosa et al, 2019 ; Raita et al, 2021 ), childhood BMI ( Au Yeung et al, 2021a ), adult BMI ( Granell et al, 2014 ; Skaaby et al, 2018 ; Xu et al, 2019 ; Sun et al, 2020 ; Au Yeung et al, 2021a ), major depressive disorder ( Mulugeta et al, 2020 ), early pubertal maturation ( Chen et al, 2020 ), age at puberty ( Minelli et al, 2018 ), estimated glomerular filtration rate ( Park et al, 2021 ), lifetime smoking ( Shen et al, 2020 ), and linoleic acid ( Zhao and Schooling, 2019 ).…”