Causal relationships between adiposity and childhood asthma: bi-directional Mendelian Randomization analysis

Chen, Yang Ching; Fan, Hsien Yu; Huang, Yue; Huang, Shih Yi; Liou, Tsan Hon; Lee, Yungling Leo

doi:10.1038/s41366-018-0160-8

Cited by 29 publications

(43 citation statements)

References 32 publications

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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

224

251

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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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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

224

251

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“…These findings highlighted the imperative to monitor BMI and control weight routinely among the asthmatic children, even in regions exhibiting a relatively low prevalence of asthma and obesity, to combat comorbidity of asthma and obesity. However, it is worth noting that the only longitudinal study [13] in China investigating the causal relationship between asthma and adiposity only showed a small effect of asthma on adiposity accumulation among children aged 9-13 years, which is inadequate to clarify the underlying causality. Thus, more longitudinal data from diverse populations will be necessary to elucidate this conundrum.…”

Section: Discussionmentioning

confidence: 99%

“…The few longitudinal studies showed that asthma was associated with higher risks of subsequent weight gain and/or obesity in children [10][11][12]. In contrast, results from other studies did not support the effect of asthma on adiposity accumulation [13] or overweight/obesity development [14]. Additionally, it is worth noting that the vast majority of existing evidence was based on data from the US [7,8,10,11] or European countries [5,6,12], where the prevalence of asthma and obesity are relatively high [15,16], conferring an uncertainty when applied to other populations.…”

Section: Introductionmentioning

confidence: 93%

“…Additionally, it is worth noting that the vast majority of existing evidence was based on data from the US [7,8,10,11] or European countries [5,6,12], where the prevalence of asthma and obesity are relatively high [15,16], conferring an uncertainty when applied to other populations. To our knowledge, only one prior study has examined the effect of asthma on adiposity among 5138 Chinese-ancestry children aged 9-13 years [13]. Given that ethnic differences do exist in the association between asthma and obesity [17], there is a key research gap in the literature.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Association between Physician-Diagnosed Asthma and Weight Status among Chinese Children: The Roles of Lifestyle Factors

Lai

Zhang

Zeng

et al. 2020

IJERPH

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Childhood asthma and obesity have posed a parallel epidemic over the past few decades. However, whether asthma diagnosis is associated with obesity, and what the roles of lifestyle factors play in this relationship, remained unclarified. This study aimed to investigate the association between asthma and weight status in Chinese children and explore the potential mediating and/or modifying roles of lifestyle factors in the association. In this cross-sectional study, 16,837 children aged 6–12 years were recruited from Guangzhou, China. Participants’ information on physician-diagnosed asthma was collected from parents, and data on physical activity, screen time, and sleeping were reported in a validated questionnaire. Height and weight were objectively measured, and weight status was classified by body mass index (BMI). Multiple logistic regression analysis and mediation analysis were used. Results showed that asthmatic children were at significantly higher risk of obesity (odds ratio (OR) 1.51, 95% confidence interval (CI) 1.03, 2.21) compared with non-asthmatic children. More importantly, this increased risk was even greater in children with moderate-to-vigorous physical activity <60 min/d and children with screen time >2 h/d (both Pinteraction < 0.05). Also, a positive relationship of asthma with overweight was found in children with screen time >2 h/d (OR 3.92, 95% CI 1.56, 9.88), while a negative association was observed between asthma and underweight in children aged 9–12 years (OR 0.23, 95% CI 0.06, 0.92). Mediation analysis indicated that these associations were not mediated by physical activity, screen time, or sleeping. The findings suggested that physician-diagnosed asthma was associated with higher risks of overweight and obesity, and these risks might be exacerbated by insufficient physical activity and prolonged screen time.

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“…Chen et al (43) carried out a bidirectional MR analysis of the direction of causation between obesity and childhood asthma in Taiwan. While the obesity genetic risk score was a significant predictor of asthma, the asthma genetic risk score did not predict obesity.…”

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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Causal relationships between adiposity and childhood asthma: bi-directional Mendelian Randomization analysis

Abstract: High adiposity may lead to asthma, whereas the effects of asthma on adiposity accumulation are likely to be small.

Cited by 29 publications

References 32 publications

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

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

Association between Physician-Diagnosed Asthma and Weight Status among Chinese Children: The Roles of Lifestyle Factors

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

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