Abstract
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: n cases = 7,009, n control = 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.
Highlights
Hematological cells play critical roles in protecting the host organism against immune assault (Li et al, 2013)
The main aim of this study is to identify novel loci and signals associated with White blood cells (WBCs) traits and assess the causal relationships between these traits and asthma using SNPs as genetic instruments
WBCc is the trait with the highest number of individuals and Baso has the lowest samples analyzed
Summary
Hematological cells play critical roles in protecting the host organism against immune assault (Li et al, 2013). White blood cells (WBCs) play a major role in both innate and adaptive immune systems, serving as the primary defense system against foreign assaults. Due to the role they play in defense and immunity, they are used as biomarkers for detecting inflammation (Gopal et al, 2012). WBCs are categorized into five subtypes based on their functions and morphology: basophils (Baso), eosinophils (Eos), lymphocytes (Lym), monocytes (Mon), and neutrophils (Neu). 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
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