Soremekun, O, Soremekun, C, Machipisa, T, Soliman, M, Nashiru, O, Chikowore, T and Fatumo, S. 2021. Genome-Wide Association and Mendelian Randomization Analysis Reveal the Causal Relationship Between White Blood Cell Subtypes and Asthma in Africans. [Online]. London School of Hygiene & Tropical Medicine, London, United Kingdom. Available from: https://doi.org/10.3389/fgene.2021.749415.s001
Soremekun, O, Soremekun, C, Machipisa, T, Soliman, M, Nashiru, O, Chikowore, T and Fatumo, S. Genome-Wide Association and Mendelian Randomization Analysis Reveal the Causal Relationship Between White Blood Cell Subtypes and Asthma in Africans [Internet]. London School of Hygiene & Tropical Medicine; 2021. Available from: https://doi.org/10.3389/fgene.2021.749415.s001
Soremekun, O, Soremekun, C, Machipisa, T, Soliman, M, Nashiru, O, Chikowore, T and Fatumo, S (2021). Genome-Wide Association and Mendelian Randomization Analysis Reveal the Causal Relationship Between White Blood Cell Subtypes and Asthma in Africans. [Data Collection]. London School of Hygiene & Tropical Medicine, London, United Kingdom. https://doi.org/10.3389/fgene.2021.749415.s001
Description
Background: White blood cell (WBC) traits and their subtypes such as basophil count (Bas), eosinophil count (Eos), lymphocyte count (Lym), monocyte count (Mon), and neutrophil counts (Neu) are known to be associated with diseases such as stroke, peripheral arterial disease, and coronary heart disease.
Methods: We meta-analyze summary statistics from genome-wide association studies in 17,802 participants from the African Partnership for Chronic Disease Research (APCDR) and African ancestry individuals from the Blood Cell Consortium (BCX2) using GWAMA. We further carried out a Bayesian fine mapping to identify causal variants driving the association with WBC subtypes. To access the causal relationship between WBC subtypes and asthma, we conducted a two-sample Mendelian randomization (MR) analysis using summary statistics of the Consortium on Asthma among African Ancestry Populations (CAAPA: ncases = 7,009, ncontrol = 7,645) as our outcome phenotype.
Results: Our metanalysis identified 269 loci at a genome-wide significant value of (p = 5 × 10−9) in a composite of the WBC subtypes while the Bayesian fine-mapping analysis identified genetic variants that are more causal than the sentinel single-nucleotide polymorphism (SNP). We found for the first time five novel genes (LOC126987/MTCO3P14, LINC01525, GAPDHP32/HSD3BP3, FLG-AS1/HMGN3P1, and TRK-CTT13-1/MGST3) not previously reported to be associated with any WBC subtype. Our MR analysis showed that Mon (IVW estimate = 0.38, CI: 0.221, 0.539, p < 0.001), Neu (IVW estimate = 0.189, CI: 0.133, 0.245, p < 0.001), and WBCc (IVW estimate = 0.185, CI: 0.108, 0.262, p < 0.001) are associated with increased risk of asthma. However, there was no evidence of causal relationship between Lym and asthma risk.
Conclusion: This study provides insight into the relationship between some WBC subtypes and asthma and potential route in the treatment of asthma and may further inform a new therapeutic approach.
| Data capture method | Unknown |
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| Date (Date published in a 3rd party system) | 2 December 2021 |
| Language(s) of written materials | English |
| Data Creators | Soremekun, O, Soremekun, C, Machipisa, T, Soliman, M, Nashiru, O, Chikowore, T and Fatumo, S |
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| LSHTM Faculty/Department | Faculty of Epidemiology and Population Health > Dept of Non-Communicable Disease Epidemiology |
| Participating Institutions | London School of Hygiene & Tropical Medicine, London, United Kingdom |
| Date Deposited | 20 Jan 2022 10:54 |
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| Last Modified | 20 Jan 2022 10:54 |
| Publisher | London School of Hygiene & Tropical Medicine |
