Genome-Wide Interaction Study of Late-Onset Asthma With Seven Environmental Factors Using a Structured Linear Mixed Model in Europeans
Asthma is among the most common chronic diseases worldwide, creating a substantial healthcare burden. In late-onset asthma, there are wide global differences in asthma prevalence and low genetic heritability. It has been suggested as evidence for genetic susceptibility to asthma triggered by exposur...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-03-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.765502/full |
| _version_ | 1818283095605903360 |
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| author | Eun Ju Baek Hae Un Jung Tae-Woong Ha Dong Jun Kim Ji Eun Lim Han Kyul Kim Ji-One Kang Bermseok Oh Bermseok Oh |
| author_facet | Eun Ju Baek Hae Un Jung Tae-Woong Ha Dong Jun Kim Ji Eun Lim Han Kyul Kim Ji-One Kang Bermseok Oh Bermseok Oh |
| author_sort | Eun Ju Baek |
| collection | DOAJ |
| description | Asthma is among the most common chronic diseases worldwide, creating a substantial healthcare burden. In late-onset asthma, there are wide global differences in asthma prevalence and low genetic heritability. It has been suggested as evidence for genetic susceptibility to asthma triggered by exposure to multiple environmental factors. Very few genome-wide interaction studies have identified gene-environment (G×E) interaction loci for asthma in adults. We evaluated genetic loci for late-onset asthma showing G×E interactions with multiple environmental factors, including alcohol intake, body mass index, insomnia, physical activity, mental status, sedentary behavior, and socioeconomic status. In gene-by-single environment interactions, we found no genome-wide significant single-nucleotide polymorphisms. However, in the gene-by-multi-environment interaction study, we identified three novel and genome-wide significant single-nucleotide polymorphisms: rs117996675, rs345749, and rs17704680. Bayes factor analysis suggested that for rs117996675 and rs17704680, body mass index is the most relevant environmental factor; for rs345749, insomnia and alcohol intake frequency are the most relevant factors in the G×E interactions of late-onset asthma. Functional annotations implicate the role of these three novel loci in regulating the immune system. In addition, the annotation for rs117996675 supports the body mass index as the most relevant environmental factor, as evidenced by the Bayes factor value. Our findings help to understand the role of the immune system in asthma and the role of environmental factors in late-onset asthma through G×E interactions. Ultimately, the enhanced understanding of asthma would contribute to better precision treatment depending on personal genetic and environmental information. |
| first_indexed | 2024-12-13T00:31:28Z |
| format | Article |
| id | doaj.art-d50cbb39641d400fbcba99e3e38a836b |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-13T00:31:28Z |
| publishDate | 2022-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-d50cbb39641d400fbcba99e3e38a836b2022-12-22T00:05:19ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-03-011310.3389/fgene.2022.765502765502Genome-Wide Interaction Study of Late-Onset Asthma With Seven Environmental Factors Using a Structured Linear Mixed Model in EuropeansEun Ju Baek0Hae Un Jung1Tae-Woong Ha2Dong Jun Kim3Ji Eun Lim4Han Kyul Kim5Ji-One Kang6Bermseok Oh7Bermseok Oh8Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, KoreaDepartment of Biomedical Science, Graduate School, Kyung Hee University, Seoul, KoreaDepartment of Biomedical Science, Graduate School, Kyung Hee University, Seoul, KoreaDepartment of Biomedical Science, Graduate School, Kyung Hee University, Seoul, KoreaDepartment of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, KoreaDepartment of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, KoreaDepartment of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, KoreaDepartment of Biomedical Science, Graduate School, Kyung Hee University, Seoul, KoreaDepartment of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, KoreaAsthma is among the most common chronic diseases worldwide, creating a substantial healthcare burden. In late-onset asthma, there are wide global differences in asthma prevalence and low genetic heritability. It has been suggested as evidence for genetic susceptibility to asthma triggered by exposure to multiple environmental factors. Very few genome-wide interaction studies have identified gene-environment (G×E) interaction loci for asthma in adults. We evaluated genetic loci for late-onset asthma showing G×E interactions with multiple environmental factors, including alcohol intake, body mass index, insomnia, physical activity, mental status, sedentary behavior, and socioeconomic status. In gene-by-single environment interactions, we found no genome-wide significant single-nucleotide polymorphisms. However, in the gene-by-multi-environment interaction study, we identified three novel and genome-wide significant single-nucleotide polymorphisms: rs117996675, rs345749, and rs17704680. Bayes factor analysis suggested that for rs117996675 and rs17704680, body mass index is the most relevant environmental factor; for rs345749, insomnia and alcohol intake frequency are the most relevant factors in the G×E interactions of late-onset asthma. Functional annotations implicate the role of these three novel loci in regulating the immune system. In addition, the annotation for rs117996675 supports the body mass index as the most relevant environmental factor, as evidenced by the Bayes factor value. Our findings help to understand the role of the immune system in asthma and the role of environmental factors in late-onset asthma through G×E interactions. Ultimately, the enhanced understanding of asthma would contribute to better precision treatment depending on personal genetic and environmental information.https://www.frontiersin.org/articles/10.3389/fgene.2022.765502/fullasthmalate-onset asthmagenome-wide interaction studystructured linear mixed modelenvironmental factor |
| spellingShingle | Eun Ju Baek Hae Un Jung Tae-Woong Ha Dong Jun Kim Ji Eun Lim Han Kyul Kim Ji-One Kang Bermseok Oh Bermseok Oh Genome-Wide Interaction Study of Late-Onset Asthma With Seven Environmental Factors Using a Structured Linear Mixed Model in Europeans Frontiers in Genetics asthma late-onset asthma genome-wide interaction study structured linear mixed model environmental factor |
| title | Genome-Wide Interaction Study of Late-Onset Asthma With Seven Environmental Factors Using a Structured Linear Mixed Model in Europeans |
| title_full | Genome-Wide Interaction Study of Late-Onset Asthma With Seven Environmental Factors Using a Structured Linear Mixed Model in Europeans |
| title_fullStr | Genome-Wide Interaction Study of Late-Onset Asthma With Seven Environmental Factors Using a Structured Linear Mixed Model in Europeans |
| title_full_unstemmed | Genome-Wide Interaction Study of Late-Onset Asthma With Seven Environmental Factors Using a Structured Linear Mixed Model in Europeans |
| title_short | Genome-Wide Interaction Study of Late-Onset Asthma With Seven Environmental Factors Using a Structured Linear Mixed Model in Europeans |
| title_sort | genome wide interaction study of late onset asthma with seven environmental factors using a structured linear mixed model in europeans |
| topic | asthma late-onset asthma genome-wide interaction study structured linear mixed model environmental factor |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.765502/full |
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