A lifecourse Mendelian randomization study uncovers age-dependent effects of adiposity on asthma risk

Helena Urquijo; Genevieve M Leyden; George Davey Smith; Tom G Richardson

doi:10.1016/j.isci.2023.108356

A lifecourse Mendelian randomization study uncovers age-dependent effects of adiposity on asthma risk

Helena Urquijo, Genevieve M Leyden, George Davey Smith, Tom G Richardson^*

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

Abstract

Evaluating the long-term consequences of childhood lifestyle factors on asthma risk can be exceptionally challenging in epidemiology given that cases are typically diagnosed at various timepoints throughout the lifecourse. In this study, we used human genetic data to evaluate the effects of childhood and adulthood adiposity on risk of pediatric (n = 13,962 cases) and adult-onset asthma (n = 26,582 cases) with a common set of controls (n = 300,671) using a technique known as lifecourse Mendelian randomization. We found that childhood adiposity directly increases risk of pediatric asthma (OR = 1.20, 95% CI = 1.03–1.37, p = 0.03), but limited evidence that it has an effect on adult-onset asthma after accounting for adiposity during adulthood (OR = 1.05, 95% CI = 0.93–1.17, p = 0.39). Conversely, there was strong evidence that adulthood adiposity increases asthma risk in midlife (OR = 1.37, 95% CI = 1.28–1.46, P = 7 × 10⁻¹²). These findings suggest that childhood and adulthood adiposity are independent risk factors for asthma at each of their corresponding timepoints in the lifecourse.

Original language	English
Article number	108356
Number of pages	7
Journal	iScience
Volume	26
Issue number	12
Early online date	29 Oct 2023
DOIs	https://doi.org/10.1016/j.isci.2023.108356
Publication status	Published - 15 Dec 2023

Bibliographical note

Funding Information: This work was supported by the Integrative Epidemiology Unit which receives funding from the UK Medical Research Council and the University of Bristol ( MC_UU_00011/1 and MC_UU_00032/03 ). HU is supported by a BHF studentship ( FS/17/60/33474 ).

Publisher Copyright: © 2023

Research Groups and Themes

Bristol Population Health Science Institute

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10.1016/j.isci.2023.108356Licence: CC BY-NC-ND

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IEU: MRC Integrative Epidemiology Unit Quinquennial renewal
Gaunt, L. F. (Principal Investigator) & Davey Smith, G. (Principal Investigator)
1/04/18 → 31/03/23
Project: Research

Cite this

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title = "A lifecourse Mendelian randomization study uncovers age-dependent effects of adiposity on asthma risk",

abstract = "Evaluating the long-term consequences of childhood lifestyle factors on asthma risk can be exceptionally challenging in epidemiology given that cases are typically diagnosed at various timepoints throughout the lifecourse. In this study, we used human genetic data to evaluate the effects of childhood and adulthood adiposity on risk of pediatric (n = 13,962 cases) and adult-onset asthma (n = 26,582 cases) with a common set of controls (n = 300,671) using a technique known as lifecourse Mendelian randomization. We found that childhood adiposity directly increases risk of pediatric asthma (OR = 1.20, 95% CI = 1.03–1.37, p = 0.03), but limited evidence that it has an effect on adult-onset asthma after accounting for adiposity during adulthood (OR = 1.05, 95% CI = 0.93–1.17, p = 0.39). Conversely, there was strong evidence that adulthood adiposity increases asthma risk in midlife (OR = 1.37, 95% CI = 1.28–1.46, P = 7 × 10−12). These findings suggest that childhood and adulthood adiposity are independent risk factors for asthma at each of their corresponding timepoints in the lifecourse.",

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note = "Funding Information: This work was supported by the Integrative Epidemiology Unit which receives funding from the UK Medical Research Council and the University of Bristol ( MC_UU_00011/1 and MC_UU_00032/03 ). HU is supported by a BHF studentship ( FS/17/60/33474 ). Publisher Copyright: {\textcopyright} 2023",

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N1 - Funding Information: This work was supported by the Integrative Epidemiology Unit which receives funding from the UK Medical Research Council and the University of Bristol ( MC_UU_00011/1 and MC_UU_00032/03 ). HU is supported by a BHF studentship ( FS/17/60/33474 ). Publisher Copyright: © 2023

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N2 - Evaluating the long-term consequences of childhood lifestyle factors on asthma risk can be exceptionally challenging in epidemiology given that cases are typically diagnosed at various timepoints throughout the lifecourse. In this study, we used human genetic data to evaluate the effects of childhood and adulthood adiposity on risk of pediatric (n = 13,962 cases) and adult-onset asthma (n = 26,582 cases) with a common set of controls (n = 300,671) using a technique known as lifecourse Mendelian randomization. We found that childhood adiposity directly increases risk of pediatric asthma (OR = 1.20, 95% CI = 1.03–1.37, p = 0.03), but limited evidence that it has an effect on adult-onset asthma after accounting for adiposity during adulthood (OR = 1.05, 95% CI = 0.93–1.17, p = 0.39). Conversely, there was strong evidence that adulthood adiposity increases asthma risk in midlife (OR = 1.37, 95% CI = 1.28–1.46, P = 7 × 10−12). These findings suggest that childhood and adulthood adiposity are independent risk factors for asthma at each of their corresponding timepoints in the lifecourse.

AB - Evaluating the long-term consequences of childhood lifestyle factors on asthma risk can be exceptionally challenging in epidemiology given that cases are typically diagnosed at various timepoints throughout the lifecourse. In this study, we used human genetic data to evaluate the effects of childhood and adulthood adiposity on risk of pediatric (n = 13,962 cases) and adult-onset asthma (n = 26,582 cases) with a common set of controls (n = 300,671) using a technique known as lifecourse Mendelian randomization. We found that childhood adiposity directly increases risk of pediatric asthma (OR = 1.20, 95% CI = 1.03–1.37, p = 0.03), but limited evidence that it has an effect on adult-onset asthma after accounting for adiposity during adulthood (OR = 1.05, 95% CI = 0.93–1.17, p = 0.39). Conversely, there was strong evidence that adulthood adiposity increases asthma risk in midlife (OR = 1.37, 95% CI = 1.28–1.46, P = 7 × 10−12). These findings suggest that childhood and adulthood adiposity are independent risk factors for asthma at each of their corresponding timepoints in the lifecourse.

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A lifecourse Mendelian randomization study uncovers age-dependent effects of adiposity on asthma risk

Abstract

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IEU: MRC Integrative Epidemiology Unit Quinquennial renewal

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