TY - JOUR
T1 - Association of inflammatory cytokines with lung function, chronic lung diseases, and COVID-19
AU - Rontogianni, Marina O.
AU - Gill, Dipender
AU - Bouras, Emmanouil
AU - Asimakopoulos, Alexandros Georgios
AU - Tzoulaki, Ioanna
AU - Karhunen, Ville
AU - Lehtimäki, Terho
AU - Raitakari, Olli
AU - Wielscher, Matthias
AU - Salomaa, Veikko
AU - Jalkanen, Sirpa
AU - Salmi, Marko
AU - Timonen, Markku
AU - Yarmolinsky, James
AU - Chen, Jing
AU - Tobin, Martin D.
AU - Izquierdo, Abril G.
AU - Herzig, Karl Heinz
AU - Ioannides, Anne E.
AU - Jarvelin, Marjo Riitta
AU - Dehghan, Abbas
AU - Tsilidis, Konstantinos K.
N1 - Publisher Copyright:
© 2024 The Author(s)
PY - 2024/10/18
Y1 - 2024/10/18
N2 - We investigated the effects of 35 inflammatory cytokines on respiratory outcomes, including COVID-19, asthma (atopic and non-atopic), chronic obstructive pulmonary disease (COPD), and pulmonary function indices, using Mendelian randomization and colocalization analyses. The emerging associations were further explored using observational analyses in the UK Biobank. We found an inverse association between genetically predicted macrophage colony stimulating factor (MCSF), soluble intercellular adhesion molecule-1 (sICAM), and soluble vascular cell adhesion molecule-1 with risk of COVID-19 outcomes. sICAM was positively associated with atopic asthma risk, whereas tumor necrosis factor-alfa showed an inverse association. A positive association was shown between interleukin-18 and COPD risk (replicated in observational analysis), whereas an inverse association was shown for interleukin-1 receptor antagonist (IL-1ra). IL-1ra and monocyte chemotactic protein-3 were positively associated with lung function indices, whereas inverse associations were shown for MCSF and interleukin-18 (replicated in observational analysis). Our results point to these cytokines as potential pharmacological targets for respiratory traits.
AB - We investigated the effects of 35 inflammatory cytokines on respiratory outcomes, including COVID-19, asthma (atopic and non-atopic), chronic obstructive pulmonary disease (COPD), and pulmonary function indices, using Mendelian randomization and colocalization analyses. The emerging associations were further explored using observational analyses in the UK Biobank. We found an inverse association between genetically predicted macrophage colony stimulating factor (MCSF), soluble intercellular adhesion molecule-1 (sICAM), and soluble vascular cell adhesion molecule-1 with risk of COVID-19 outcomes. sICAM was positively associated with atopic asthma risk, whereas tumor necrosis factor-alfa showed an inverse association. A positive association was shown between interleukin-18 and COPD risk (replicated in observational analysis), whereas an inverse association was shown for interleukin-1 receptor antagonist (IL-1ra). IL-1ra and monocyte chemotactic protein-3 were positively associated with lung function indices, whereas inverse associations were shown for MCSF and interleukin-18 (replicated in observational analysis). Our results point to these cytokines as potential pharmacological targets for respiratory traits.
KW - Association analysis
KW - Disease
KW - Health sciences
KW - Respiratory medicine
U2 - 10.1016/j.isci.2024.110704
DO - 10.1016/j.isci.2024.110704
M3 - Article
AN - SCOPUS:85207743948
SN - 2589-0042
VL - 27
JO - Iscience
JF - Iscience
IS - 10
M1 - 110704
ER -