Genome-Wide Association and Mendelian Randomization Analysis Reveal the Causal Relationship Between White Blood Cell Subtypes and Asthma in Africans

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 diseas...

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Autores principales:	Opeyemi Soremekun, Chisom Soremekun, Tafadzwa Machipisa, Mahmoud Soliman, Oyekanmi Nashiru, Tinashe Chikowore, Segun Fatumo
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	white blood cell traits asthma metanalysis Mendelian randomization fine mapping Genetics QH426-470
Acceso en línea:	https://doaj.org/article/5308e30dbb4d4b22b582bcaa719452b0
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spelling	oai:doaj.org-article:5308e30dbb4d4b22b582bcaa719452b02021-12-02T09:52:03ZGenome-Wide Association and Mendelian Randomization Analysis Reveal the Causal Relationship Between White Blood Cell Subtypes and Asthma in Africans1664-802110.3389/fgene.2021.749415https://doaj.org/article/5308e30dbb4d4b22b582bcaa719452b02021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fgene.2021.749415/fullhttps://doaj.org/toc/1664-8021Background: 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.Opeyemi SoremekunChisom SoremekunChisom SoremekunTafadzwa MachipisaTafadzwa MachipisaMahmoud SolimanOyekanmi NashiruTinashe ChikoworeTinashe ChikoworeSegun FatumoSegun FatumoSegun FatumoFrontiers Media S.A.articlewhite blood cell traitsasthmametanalysisMendelian randomizationfine mappingGeneticsQH426-470ENFrontiers in Genetics, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	white blood cell traits asthma metanalysis Mendelian randomization fine mapping Genetics QH426-470
spellingShingle	white blood cell traits asthma metanalysis Mendelian randomization fine mapping Genetics QH426-470 Opeyemi Soremekun Chisom Soremekun Chisom Soremekun Tafadzwa Machipisa Tafadzwa Machipisa Mahmoud Soliman Oyekanmi Nashiru Tinashe Chikowore Tinashe Chikowore Segun Fatumo Segun Fatumo Segun Fatumo Genome-Wide Association and Mendelian Randomization Analysis Reveal the Causal Relationship Between White Blood Cell Subtypes and Asthma in Africans
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.
format	article
author	Opeyemi Soremekun Chisom Soremekun Chisom Soremekun Tafadzwa Machipisa Tafadzwa Machipisa Mahmoud Soliman Oyekanmi Nashiru Tinashe Chikowore Tinashe Chikowore Segun Fatumo Segun Fatumo Segun Fatumo
author_facet	Opeyemi Soremekun Chisom Soremekun Chisom Soremekun Tafadzwa Machipisa Tafadzwa Machipisa Mahmoud Soliman Oyekanmi Nashiru Tinashe Chikowore Tinashe Chikowore Segun Fatumo Segun Fatumo Segun Fatumo
author_sort	Opeyemi Soremekun
title	Genome-Wide Association and Mendelian Randomization Analysis Reveal the Causal Relationship Between White Blood Cell Subtypes and Asthma in Africans
title_short	Genome-Wide Association and Mendelian Randomization Analysis Reveal the Causal Relationship Between White Blood Cell Subtypes and Asthma in Africans
title_full	Genome-Wide Association and Mendelian Randomization Analysis Reveal the Causal Relationship Between White Blood Cell Subtypes and Asthma in Africans
title_fullStr	Genome-Wide Association and Mendelian Randomization Analysis Reveal the Causal Relationship Between White Blood Cell Subtypes and Asthma in Africans
title_full_unstemmed	Genome-Wide Association and Mendelian Randomization Analysis Reveal the Causal Relationship Between White Blood Cell Subtypes and Asthma in Africans
title_sort	genome-wide association and mendelian randomization analysis reveal the causal relationship between white blood cell subtypes and asthma in africans
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/5308e30dbb4d4b22b582bcaa719452b0
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Genome-Wide Association and Mendelian Randomization Analysis Reveal the Causal Relationship Between White Blood Cell Subtypes and Asthma in Africans

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