In this section
@article{Hamilton:2023:10.1016/j.ijid.2023.02.008,
author = {Hamilton, F and Mitchell, R and Constantinescu, A and Hughes, D and Cunnington, A and Ghazal, P and Timpson, NJ},
doi = {10.1016/j.ijid.2023.02.008},
journal = {International Journal of Infectious Diseases},
pages = {251--259},
title = {The effect of IL-6 signalling on severe malaria: a Mendelian randomisation analysis},
url = {http://dx.doi.org/10.1016/j.ijid.2023.02.008},
volume = {129},
year = {2023}
}
TY - JOUR
AB - ObjectivesSevere malaria remains a deadly disease for many young children in low- and middle-income countries. Levels of interleukin (IL)-6 have been shown to identify cases of severe malaria and associate with severity, but it is unknown if this association is causal.MethodsA single nucleotide polymorphism (SNP; rs2228145) in the IL-6 receptor was chosen as a genetic variant that is known to alter IL-6 signaling. We tested this, then took this forward as an instrument to perform Mendelian randomization (MR) in MalariaGEN, a large cohort study of patients with severe malaria at 11 worldwide sites.ResultsIn MR analyses using rs2228145, we did not identify an effect of decreased IL-6 signaling on severe malaria (odds ratio 1.14, 95% confidence interval 0.56-2.34, P = 0.713). The estimates of the association with any severe malaria subphenotype were similarly null, although with some imprecision. Further analyses using other MR approaches had similar results.ConclusionThese analyses do not support a causal role for IL-6 signaling in the development of severe malaria. This result suggests IL-6 may not be causal for severe outcomes in malaria, and that therapeutic manipulation of IL-6 is unlikely to be a suitable treatment for severe malaria.
AU - Hamilton,F
AU - Mitchell,R
AU - Constantinescu,A
AU - Hughes,D
AU - Cunnington,A
AU - Ghazal,P
AU - Timpson,NJ
DO - 10.1016/j.ijid.2023.02.008
EP - 259
PY - 2023///
SN - 1201-9712
SP - 251
TI - The effect of IL-6 signalling on severe malaria: a Mendelian randomisation analysis
T2 - International Journal of Infectious Diseases
UR - http://dx.doi.org/10.1016/j.ijid.2023.02.008
UR - https://www.ncbi.nlm.nih.gov/pubmed/36801374
UR - http://sciencedirect.com/science/article/pii/S1201971223000565?via%3Dihub
UR - http://hdl.handle.net/10044/1/102177
VL - 129
ER -
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