File Download
Links for fulltext
(May Require Subscription)
- Publisher Website: 10.1080/15412555.2021.1955848
- Scopus: eid_2-s2.0-85111880287
- PMID: 34348529
- WOS: WOS:000681244200001
- Find via
Supplementary
- Citations:
- Appears in Collections:
Article: Genetic Evidence on the Association of Interleukin (IL)-1-Mediated Chronic Inflammation with Airflow Obstruction: A Mendelian Randomization Study
Title | Genetic Evidence on the Association of Interleukin (IL)-1-Mediated Chronic Inflammation with Airflow Obstruction: A Mendelian Randomization Study |
---|---|
Authors | |
Keywords | Airflow obstruction IL-1 IL-1 receptors IL-1 receptor antagonists Mendelian randomization |
Issue Date | 2021 |
Publisher | Taylor & Francis Inc. The Journal's web site is located at https://www.tandfonline.com/journals/icop20 |
Citation | COPD: journal of chronic obstructive pulmonary disease, 2021, v. 18 n. 4, p. 432-442 How to Cite? |
Abstract | Preclinical studies suggest interleukin (IL)-1α/β is involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, recent trials of anti-IL-1 therapies showed limited benefit for COPD. To clarify, we primarily examined total and direct effects of IL-1 and its receptors/coreceptors/receptor antagonists (IL-1/IL-1Rs) on airflow obstruction (AO) using Mendelian randomization (MR), and secondarily explored reverse causation using bidirectional MR. We selected independent cis protein quantitative trait loci (cis-pQTLs) as genetic instruments for IL-1/IL-1Rs from two proteomic genome-wide association studies (n = 11,594) of European ancestry (mean age ∼47 years). We applied those cis-pQTLs to the International COPD Genetics Consortium (n = 15,256 cases, 47,936 controls) of ∼81.9% European descent (∼57 years). No IL-1/IL-1Rs were significantly associated with AO after correction for multiple testing. However, a higher genetically predicted IL-1 receptor antagonist (IL-1Ra) was nominally associated with a 20% reduction in AO risk using univariable MR, with a larger direct effect (∼31%, i.e. not via IL-1α/β) using multivariable MR. Furthermore, higher total IL-18 binding protein (IL-18BP) was nominally associated with lower AO. Nominal total effects were also noted for higher IL-1α with lower AO and higher IL-1R1 with higher AO. Higher IL-1Ra and IL-18BP might have a role in preventing AO, but need to be contextualized.
Supplemental data for this article is available online at https://doi.org/10.1080/15412555.2021.1955848 . |
Persistent Identifier | http://hdl.handle.net/10722/309301 |
ISSN | 2021 Impact Factor: 2.069 2020 SCImago Journal Rankings: 0.922 |
ISI Accession Number ID |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Yang, Z | - |
dc.contributor.author | Schooling, CM | - |
dc.contributor.author | Kwok, MK | - |
dc.date.accessioned | 2021-12-29T02:13:07Z | - |
dc.date.available | 2021-12-29T02:13:07Z | - |
dc.date.issued | 2021 | - |
dc.identifier.citation | COPD: journal of chronic obstructive pulmonary disease, 2021, v. 18 n. 4, p. 432-442 | - |
dc.identifier.issn | 1541-2555 | - |
dc.identifier.uri | http://hdl.handle.net/10722/309301 | - |
dc.description.abstract | Preclinical studies suggest interleukin (IL)-1α/β is involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, recent trials of anti-IL-1 therapies showed limited benefit for COPD. To clarify, we primarily examined total and direct effects of IL-1 and its receptors/coreceptors/receptor antagonists (IL-1/IL-1Rs) on airflow obstruction (AO) using Mendelian randomization (MR), and secondarily explored reverse causation using bidirectional MR. We selected independent cis protein quantitative trait loci (cis-pQTLs) as genetic instruments for IL-1/IL-1Rs from two proteomic genome-wide association studies (n = 11,594) of European ancestry (mean age ∼47 years). We applied those cis-pQTLs to the International COPD Genetics Consortium (n = 15,256 cases, 47,936 controls) of ∼81.9% European descent (∼57 years). No IL-1/IL-1Rs were significantly associated with AO after correction for multiple testing. However, a higher genetically predicted IL-1 receptor antagonist (IL-1Ra) was nominally associated with a 20% reduction in AO risk using univariable MR, with a larger direct effect (∼31%, i.e. not via IL-1α/β) using multivariable MR. Furthermore, higher total IL-18 binding protein (IL-18BP) was nominally associated with lower AO. Nominal total effects were also noted for higher IL-1α with lower AO and higher IL-1R1 with higher AO. Higher IL-1Ra and IL-18BP might have a role in preventing AO, but need to be contextualized. Supplemental data for this article is available online at https://doi.org/10.1080/15412555.2021.1955848 . | - |
dc.language | eng | - |
dc.publisher | Taylor & Francis Inc. The Journal's web site is located at https://www.tandfonline.com/journals/icop20 | - |
dc.relation.ispartof | COPD: journal of chronic obstructive pulmonary disease | - |
dc.rights | This is an Accepted Manuscript of an article published by Taylor & Francis in COPD: journal of chronic obstructive pulmonary disease on 04 Aug 2021, available online: https://doi.org/10.1080/15412555.2021.1955848 | - |
dc.subject | Airflow obstruction | - |
dc.subject | IL-1 | - |
dc.subject | IL-1 receptors | - |
dc.subject | IL-1 receptor antagonists | - |
dc.subject | Mendelian randomization | - |
dc.title | Genetic Evidence on the Association of Interleukin (IL)-1-Mediated Chronic Inflammation with Airflow Obstruction: A Mendelian Randomization Study | - |
dc.type | Article | - |
dc.identifier.email | Schooling, CM: cms1@hkucc.hku.hk | - |
dc.identifier.email | Kwok, MK: maggiek@hku.hk | - |
dc.identifier.authority | Schooling, CM=rp00504 | - |
dc.identifier.authority | Kwok, MK=rp02051 | - |
dc.description.nature | postprint | - |
dc.identifier.doi | 10.1080/15412555.2021.1955848 | - |
dc.identifier.pmid | 34348529 | - |
dc.identifier.scopus | eid_2-s2.0-85111880287 | - |
dc.identifier.hkuros | 331354 | - |
dc.identifier.volume | 18 | - |
dc.identifier.issue | 4 | - |
dc.identifier.spage | 432 | - |
dc.identifier.epage | 442 | - |
dc.identifier.isi | WOS:000681244200001 | - |
dc.publisher.place | United States | - |