Association Between Environmental Factors and Asthma Using Mendelian Randomization: Increased Effect of Body Mass Index on Adult-Onset Moderate-to-Severe Asthma Subtypes
Although asthma is one of the most common chronic diseases throughout all age groups, its etiology remains unknown, primarily due to its heterogeneous characteristics. We examined the causal effects of various environmental factors on asthma using Mendelian randomization and determined whether the s...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-05-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2021.639905/full |
| _version_ | 1819068380565471232 |
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| author | Tae-Woong Ha Hae-Un Jung Dong Jun Kim Eun Ju Baek Won Jun Lee Ji Eun Lim Han Kyul Kim Ji-One Kang Bermseok Oh |
| author_facet | Tae-Woong Ha Hae-Un Jung Dong Jun Kim Eun Ju Baek Won Jun Lee Ji Eun Lim Han Kyul Kim Ji-One Kang Bermseok Oh |
| author_sort | Tae-Woong Ha |
| collection | DOAJ |
| description | Although asthma is one of the most common chronic diseases throughout all age groups, its etiology remains unknown, primarily due to its heterogeneous characteristics. We examined the causal effects of various environmental factors on asthma using Mendelian randomization and determined whether the susceptibility to asthma due to the causal effect of a risk factor differs between asthma subtypes, based on age of onset, severity of asthma, and sex. We performed Mendelian randomization analyses (inverse variance weighted, weighted median, and generalized summary-data-based Mendelian randomization) using UK Biobank data to estimate the causal effects of 69 environmental factors on asthma. Additional sensitivity analyses (MR-Egger regression, Cochran’s Q test, clumping, and reverse Mendelian randomization) were performed to ensure minimal or no pleiotropy. For confirmation, two-sample setting analyses were replicated using BMI SNPs that had been reported by a meta-genome-wide association study in Japanese and European (GIANT) populations and a genome-wide association study in control individuals from the UK Biobank. We found that BMI causally affects the development of asthma and that the adult-onset moderate-to-severe asthma subtype is the most susceptible to causal inference by BMI. Further, it is likely that the female subtype is more susceptible to BMI than males among adult asthma cases. Our findings provide evidence that obesity is a considerable risk factor in asthma patients, particularly in adult-onset moderate-to-severe asthma cases, and that weight loss is beneficial for reducing the burden of asthma. |
| first_indexed | 2024-12-21T16:33:14Z |
| format | Article |
| id | doaj.art-5443597d67ae42a49b4d6bf4ab670040 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-21T16:33:14Z |
| publishDate | 2021-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-5443597d67ae42a49b4d6bf4ab6700402022-12-21T18:57:17ZengFrontiers Media S.A.Frontiers in Genetics1664-80212021-05-011210.3389/fgene.2021.639905639905Association Between Environmental Factors and Asthma Using Mendelian Randomization: Increased Effect of Body Mass Index on Adult-Onset Moderate-to-Severe Asthma SubtypesTae-Woong Ha0Hae-Un Jung1Dong Jun Kim2Eun Ju Baek3Won Jun Lee4Ji Eun Lim5Han Kyul Kim6Ji-One Kang7Bermseok Oh8Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, South KoreaDepartment of Biomedical Science, Graduate School, Kyung Hee University, Seoul, South KoreaDepartment of Biomedical Science, Graduate School, Kyung Hee University, Seoul, South KoreaDepartment of Biomedical Science, Graduate School, Kyung Hee University, Seoul, South KoreaDepartment of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, South KoreaDepartment of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, South KoreaDepartment of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, South KoreaDepartment of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, South KoreaDepartment of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, South KoreaAlthough asthma is one of the most common chronic diseases throughout all age groups, its etiology remains unknown, primarily due to its heterogeneous characteristics. We examined the causal effects of various environmental factors on asthma using Mendelian randomization and determined whether the susceptibility to asthma due to the causal effect of a risk factor differs between asthma subtypes, based on age of onset, severity of asthma, and sex. We performed Mendelian randomization analyses (inverse variance weighted, weighted median, and generalized summary-data-based Mendelian randomization) using UK Biobank data to estimate the causal effects of 69 environmental factors on asthma. Additional sensitivity analyses (MR-Egger regression, Cochran’s Q test, clumping, and reverse Mendelian randomization) were performed to ensure minimal or no pleiotropy. For confirmation, two-sample setting analyses were replicated using BMI SNPs that had been reported by a meta-genome-wide association study in Japanese and European (GIANT) populations and a genome-wide association study in control individuals from the UK Biobank. We found that BMI causally affects the development of asthma and that the adult-onset moderate-to-severe asthma subtype is the most susceptible to causal inference by BMI. Further, it is likely that the female subtype is more susceptible to BMI than males among adult asthma cases. Our findings provide evidence that obesity is a considerable risk factor in asthma patients, particularly in adult-onset moderate-to-severe asthma cases, and that weight loss is beneficial for reducing the burden of asthma.https://www.frontiersin.org/articles/10.3389/fgene.2021.639905/fullasthmaenvironmental factorsbody mass indexmendelian randomizationmoderate-to-severe asthma |
| spellingShingle | Tae-Woong Ha Hae-Un Jung Dong Jun Kim Eun Ju Baek Won Jun Lee Ji Eun Lim Han Kyul Kim Ji-One Kang Bermseok Oh Association Between Environmental Factors and Asthma Using Mendelian Randomization: Increased Effect of Body Mass Index on Adult-Onset Moderate-to-Severe Asthma Subtypes Frontiers in Genetics asthma environmental factors body mass index mendelian randomization moderate-to-severe asthma |
| title | Association Between Environmental Factors and Asthma Using Mendelian Randomization: Increased Effect of Body Mass Index on Adult-Onset Moderate-to-Severe Asthma Subtypes |
| title_full | Association Between Environmental Factors and Asthma Using Mendelian Randomization: Increased Effect of Body Mass Index on Adult-Onset Moderate-to-Severe Asthma Subtypes |
| title_fullStr | Association Between Environmental Factors and Asthma Using Mendelian Randomization: Increased Effect of Body Mass Index on Adult-Onset Moderate-to-Severe Asthma Subtypes |
| title_full_unstemmed | Association Between Environmental Factors and Asthma Using Mendelian Randomization: Increased Effect of Body Mass Index on Adult-Onset Moderate-to-Severe Asthma Subtypes |
| title_short | Association Between Environmental Factors and Asthma Using Mendelian Randomization: Increased Effect of Body Mass Index on Adult-Onset Moderate-to-Severe Asthma Subtypes |
| title_sort | association between environmental factors and asthma using mendelian randomization increased effect of body mass index on adult onset moderate to severe asthma subtypes |
| topic | asthma environmental factors body mass index mendelian randomization moderate-to-severe asthma |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2021.639905/full |
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