Unspecified asthma, childhood-onset, and adult-onset asthma have different causal genes: a Mendelian randomization analysis
IntroductionAsthma is a heterogeneous condition that is characterized by reversible airway obstruction. Childhood-onset asthma (COA) and adult-onset asthma (AOA) are two prominent asthma subtypes, each with unique etiological factors and prognosis, which suggests the existence of both shared and dis...
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Frontiers Media S.A.
2024-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1412032/full |
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| author | Roan E. Zaied Sreemol Gokuladhas Caroline Walker Justin M. O’Sullivan Justin M. O’Sullivan Justin M. O’Sullivan Justin M. O’Sullivan Justin M. O’Sullivan |
| author_facet | Roan E. Zaied Sreemol Gokuladhas Caroline Walker Justin M. O’Sullivan Justin M. O’Sullivan Justin M. O’Sullivan Justin M. O’Sullivan Justin M. O’Sullivan |
| author_sort | Roan E. Zaied |
| collection | DOAJ |
| description | IntroductionAsthma is a heterogeneous condition that is characterized by reversible airway obstruction. Childhood-onset asthma (COA) and adult-onset asthma (AOA) are two prominent asthma subtypes, each with unique etiological factors and prognosis, which suggests the existence of both shared and distinct risk factors.MethodsHere, we employed a two-sample Mendelian randomization analysis to elucidate the causal association between genes within lung and whole-blood-specific gene regulatory networks (GRNs) and the development of unspecified asthma, COA, and AOA using the Wald ratio method. Lung and whole blood-specific GRNs, encompassing spatial eQTLs (instrumental variables) and their target genes (exposures), were utilized as exposure data. Genome-wide association studies for unspecified asthma, COA, and AOA were used as outcome data in this investigation. ResultsWe identified 101 genes that were causally linked to unspecified asthma, 39 genes causally associated with COA, and ten genes causally associated with AOA. Among the identified genes, 29 were shared across some, or all of the asthma subtypes. Of the identified causal genes, ORMDL3 had the strongest causal association with both unspecified asthma (OR: 1.49; 95% CI:1.42-1.57; p=7.30x10-51) and COA (OR: 3.37; 95% CI: 3.02-3.76; p=1.95x10-102), whereas PEBP1P3 had the strongest causal association with AOA (OR: 1.28; 95% CI: 1.16-1.41; p=0.007).DiscussionThis study identified shared and unique genetic factors causally associated with different asthma subtypes. In so doing, our study emphasizes the need to move beyond perceiving asthma as a singular condition to enable the development of therapeutic interventions that target sub-type specific causal genes. |
| format | Article |
| id | doaj-art-0aae16fc15ec4d24ae09f30c1fd9a6c8 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-0aae16fc15ec4d24ae09f30c1fd9a6c82024-11-19T06:15:34ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-11-011510.3389/fimmu.2024.14120321412032Unspecified asthma, childhood-onset, and adult-onset asthma have different causal genes: a Mendelian randomization analysisRoan E. Zaied0Sreemol Gokuladhas1Caroline Walker2Justin M. O’Sullivan3Justin M. O’Sullivan4Justin M. O’Sullivan5Justin M. O’Sullivan6Justin M. O’Sullivan7The Liggins Institute, The University of Auckland, Auckland, New ZealandThe Liggins Institute, The University of Auckland, Auckland, New ZealandFaculty of Medical and Health Sciences, The University of Auckland, Auckland, New ZealandThe Liggins Institute, The University of Auckland, Auckland, New ZealandThe Maurice Wilkins Centre, The University of Auckland, Auckland, New ZealandAustralian Parkinsons Mission, Garvan Institute of Medical Research, Sydney, NSW, AustraliaMRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, United KingdomSingapore Institute for Clinical Sciences, Agency for Science Technology and Research, Singapore, SingaporeIntroductionAsthma is a heterogeneous condition that is characterized by reversible airway obstruction. Childhood-onset asthma (COA) and adult-onset asthma (AOA) are two prominent asthma subtypes, each with unique etiological factors and prognosis, which suggests the existence of both shared and distinct risk factors.MethodsHere, we employed a two-sample Mendelian randomization analysis to elucidate the causal association between genes within lung and whole-blood-specific gene regulatory networks (GRNs) and the development of unspecified asthma, COA, and AOA using the Wald ratio method. Lung and whole blood-specific GRNs, encompassing spatial eQTLs (instrumental variables) and their target genes (exposures), were utilized as exposure data. Genome-wide association studies for unspecified asthma, COA, and AOA were used as outcome data in this investigation. ResultsWe identified 101 genes that were causally linked to unspecified asthma, 39 genes causally associated with COA, and ten genes causally associated with AOA. Among the identified genes, 29 were shared across some, or all of the asthma subtypes. Of the identified causal genes, ORMDL3 had the strongest causal association with both unspecified asthma (OR: 1.49; 95% CI:1.42-1.57; p=7.30x10-51) and COA (OR: 3.37; 95% CI: 3.02-3.76; p=1.95x10-102), whereas PEBP1P3 had the strongest causal association with AOA (OR: 1.28; 95% CI: 1.16-1.41; p=0.007).DiscussionThis study identified shared and unique genetic factors causally associated with different asthma subtypes. In so doing, our study emphasizes the need to move beyond perceiving asthma as a singular condition to enable the development of therapeutic interventions that target sub-type specific causal genes.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1412032/fullMendelian randomizationchildhood-onset asthmaadult-onset asthmagene regulatory networksSNP functiongenetic risk |
| spellingShingle | Roan E. Zaied Sreemol Gokuladhas Caroline Walker Justin M. O’Sullivan Justin M. O’Sullivan Justin M. O’Sullivan Justin M. O’Sullivan Justin M. O’Sullivan Unspecified asthma, childhood-onset, and adult-onset asthma have different causal genes: a Mendelian randomization analysis Frontiers in Immunology Mendelian randomization childhood-onset asthma adult-onset asthma gene regulatory networks SNP function genetic risk |
| title | Unspecified asthma, childhood-onset, and adult-onset asthma have different causal genes: a Mendelian randomization analysis |
| title_full | Unspecified asthma, childhood-onset, and adult-onset asthma have different causal genes: a Mendelian randomization analysis |
| title_fullStr | Unspecified asthma, childhood-onset, and adult-onset asthma have different causal genes: a Mendelian randomization analysis |
| title_full_unstemmed | Unspecified asthma, childhood-onset, and adult-onset asthma have different causal genes: a Mendelian randomization analysis |
| title_short | Unspecified asthma, childhood-onset, and adult-onset asthma have different causal genes: a Mendelian randomization analysis |
| title_sort | unspecified asthma childhood onset and adult onset asthma have different causal genes a mendelian randomization analysis |
| topic | Mendelian randomization childhood-onset asthma adult-onset asthma gene regulatory networks SNP function genetic risk |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1412032/full |
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