Estimating the causal effect of body mass index on hay fever, asthma and lung function using Mendelian randomization

Skaaby, Tea; Taylor, Amy E; Thuesen, Betina Heinsbæk; Jacobsen, Rikke Kart; Friedrich, Nele; Møllehave, Line Tang; Hansen, Susanne; Larsen, Sofus C.; Völker, Uwe; Nauck, Matthias; Völzke, Henry; Hansen, Torben; Pedersen, Oluf; Jørgensen, Torben; Paternoster, Lavinia; Munafò, Marcus R.; Grarup, Niels; Linneberg, Allan

doi:10.1111/all.13242

Cited by 48 publications

(55 citation statements)

References 72 publications

(108 reference statements)

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“…For example, the estimated effect of BMI on later-onset asthma was significant, with an OR of 1.21 (P 5 6.3 3 10 27 ), but the estimated effect of later-onset asthma on BMI was not (OR 5 1.00, P 5 .70); the OR in the former case represents the increase in the odds of having asthma per SD increase in BMI. Our estimated causal effect of BMI on asthma was comparable with that obtained by Skaaby et al 39 Because BMI and asthma are polygenic traits, 11,31 inferred causal relationships between them are prone to confounding caused by pleiotropy. Therefore we also applied the LCV method, a method robust to pleiotropy confounding, to infer the GCP between BMI and asthma phenotypes.…”

Section: Causal Inferencesupporting

confidence: 88%

Shared genetic and experimental links between obesity-related traits and asthma subtypes in UK Biobank

Zhu

Guo

Shi³

et al. 2020

Journal of Allergy and Clinical Immunology

278

241

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Section: Causal Inferencesupporting

confidence: 88%

Shared genetic and experimental links between obesity-related traits and asthma subtypes in UK Biobank

Zhu

Guo

Shi³

et al. 2020

Journal of Allergy and Clinical Immunology

278

241

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“…As highlighted above, a significant genetic correlation might arise because of a causal effect of these risk factors on asthma risk. [83][84][85][86] At least for obesity, such a causal effect does not appear to extend to other allergies, 87 which could potentially explain the difference in genetic correlation between AOA and COA.…”

Section: Discussionmentioning

confidence: 99%

Genetic Architectures of Childhood- and Adult-Onset Asthma Are Partly Distinct

Ferreira

Mathur

Vonk

et al. 2019

The American Journal of Human Genetics

219

240

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The extent to which genetic risk factors are shared between childhood-onset (COA) and adult-onset (AOA) asthma has not been estimated. On the basis of data from the UK Biobank study (n ¼ 447,628), we found that the variance in disease liability explained by common variants is higher for COA (onset at ages between 0 and 19 years; h 2 g ¼ 25.6%) than for AOA (onset at ages between 20 and 60 years; h 2 g ¼ 10.6%). The genetic correlation (r g ) between COA and AOA was 0.67. Variation in age of onset among COA-affected individuals had a low heritability (h 2 g ¼ 5%), which we confirmed in independent studies and also among AOA-affected individuals. To identify subtype-specific genetic associations, we performed a genome-wide association study (GWAS) in the UK Biobank for COA (13,962 affected individuals) and a separate GWAS for AOA (26,582 affected individuals) by using a common set of 300,671 controls for both studies. We identified 123 independent associations for COA and 56 for AOA (37 overlapped); of these, 98 and 34, respectively, were reproducible in an independent study (n ¼ 262,767). Collectively, 28 associations were not previously reported. For 96 COA-associated variants, including five variants that represent COA-specific risk factors, the risk allele was more common in COA-than in AOA-affected individuals. Conversely, we identified three variants that are stronger risk factors for AOA. Variants associated with obesity and smoking had a stronger contribution to the risk of AOA than to the risk of COA. Lastly, we identified 109 likely target genes of the associated variants, primarily on the basis of correlated expression quantitative trait loci (up to n ¼ 31,684). GWAS informed by age of onset can identify subtype-specific risk variants, which can help us understand differences in pathophysiology between COA and AOA and so can be informative for drug development.

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“…Granell et al (44) similarly estimated the causal relative risk for the effect of BMI on asthma at 1.55 per kg/m 2 , slightly more strongly for non-atopic childhood asthma. In 162124 adults from European studies (45), the causal OR for BMI on asthma was 1.07 (−9 ml FEV1, 16 ml FVC). There was no causal effect on allergic sensitization or serum IgE level-despite a positive phenotypic correlation between IgE and overweight in their study population.…”

Section: Mendelian Randomization Studiesmentioning

confidence: 99%

Genetics and Gene-Environment Interactions in Childhood and Adult Onset Asthma

Morales

Duffy

2019

Front. Pediatr.

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Asthma is a heterogeneous disease that results from the complex interaction between genetic factors and environmental exposures that occur at critical periods throughout life. It seems plausible to regard childhood-onset and adult-onset asthma as different entities, each with a different pathophysiology, trajectory, and outcome. This review provides an overview about the role of genetics and gene-environment interactions in these two conditions. Looking at the genetic overlap between childhood and adult onset disease gives one window into whether there is a correlation, as well as to mechanism. A second window is offered by the genetics of the relationship between each type of asthma and other phenotypes e.g., obesity, chronic obstructive pulmonary disease (COPD), atopy, vitamin D levels, and inflammatory and immune status; and third, the genetic-specific responses to the many environmental exposures that influence risk throughout life, and particularly those that occur during early-life development. These represent a large number of possible combinations of genetic and environmental factors, at least 150 known genetic loci vs. tobacco smoke, outdoor air pollutants, indoor exposures, farming environment, and microbial exposures. Considering time of asthma onset extends the two-dimensional problem of gene-environment interactions to a three-dimensional problem, since identified gene-environment interactions seldom replicate for childhood and adult asthma, which suggests that asthma susceptibility to environmental exposures may biologically differ from early life to adulthood as a result of different pathways and mechanisms of the disease.

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Estimating the causal effect of body mass index on hay fever, asthma and lung function using Mendelian randomization

Abstract: The results support the conclusion that increasing BMI is causally related to higher prevalence of asthma and decreased lung function, but not with hay fever or biomarkers of allergy.

Cited by 48 publications

References 72 publications

Shared genetic and experimental links between obesity-related traits and asthma subtypes in UK Biobank

Shared genetic and experimental links between obesity-related traits and asthma subtypes in UK Biobank

Genetic Architectures of Childhood- and Adult-Onset Asthma Are Partly Distinct

Genetics and Gene-Environment Interactions in Childhood and Adult Onset Asthma

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