Mendelian randomization study highlights the role of hematological traits on Type-2 diabetes mellitus in African ancestry individuals
IntroductionObservational studies have identified associations between hematological traits and type-2 diabetes mellitus (T2D). However, it is difficult to infer causal effects due to the potential of confounding. Our study utilizes the Mendelian randomization (MR) approach to address the above limi...
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2025-03-01
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| author | Chisom Soremekun Chisom Soremekun Chisom Soremekun Chisom Soremekun Daudi Jjingo Daudi Jjingo Daudi Jjingo David Kateete Oyekanmi Nash Dorothea Nitsch Moffat Nyirenda Moffat Nyirenda Dipender Gill Eleftheria Zeggini Eleftheria Zeggini Harald Grallert Harald Grallert Annette Peters Annette Peters Annette Peters Tinashe Chikowore Tinashe Chikowore Chiara Batini Chiara Batini Opeyemi Soremekun Opeyemi Soremekun Segun Fatumo Segun Fatumo |
| author_facet | Chisom Soremekun Chisom Soremekun Chisom Soremekun Chisom Soremekun Daudi Jjingo Daudi Jjingo Daudi Jjingo David Kateete Oyekanmi Nash Dorothea Nitsch Moffat Nyirenda Moffat Nyirenda Dipender Gill Eleftheria Zeggini Eleftheria Zeggini Harald Grallert Harald Grallert Annette Peters Annette Peters Annette Peters Tinashe Chikowore Tinashe Chikowore Chiara Batini Chiara Batini Opeyemi Soremekun Opeyemi Soremekun Segun Fatumo Segun Fatumo |
| author_sort | Chisom Soremekun |
| collection | DOAJ |
| description | IntroductionObservational studies have identified associations between hematological traits and type-2 diabetes mellitus (T2D). However, it is difficult to infer causal effects due to the potential of confounding. Our study utilizes the Mendelian randomization (MR) approach to address the above limitation and investigate the causal effect of hematological traits such as white blood cell (WBC), platelets (PLT), and red blood cell (RBC) on T2D in individuals of African ancestry.MethodsThe participating cohorts included participants of African ancestry in the Blood Cell consortium and the Million Veteran Program dataset. Using GWAS summary statistics, we applied a univariable and multivariable Two-sample MR to estimate the causal relationship between hematological traits and T2D.ResultsIn the main IVW MR estimates, genetically predicted levels of mean corpuscular hemoglobin concentration (MCHC), mean corpuscular hemoglobin (MCH), and mean corpuscular volume (MCV) were associated with decreased risk of T2D. We also observed a decreased risk of T2D with genetically predicted total WBC count and neutrophil count (NEU), for the WBC traits. The multivariable analysis further supported the direct associations of genetically predicted MCH, MCHC, and MCV levels with a decreased risk of T2D. For the European ancestry, a similar pattern of association was observed for MCH and MCV.DiscussionThese findings indicate that hematological traits may differentially play a role in the development of T2D and be affected by T2D. However, further research is needed to validate and explore the biological pathways and mechanisms involved in these associations. |
| format | Article |
| id | doaj-art-8848ef2157fa4890b0d598fc59612ea0 |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-03-01 |
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| spelling | doaj-art-8848ef2157fa4890b0d598fc59612ea02025-08-20T03:41:01ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-03-011610.3389/fphar.2025.14369721436972Mendelian randomization study highlights the role of hematological traits on Type-2 diabetes mellitus in African ancestry individualsChisom Soremekun0Chisom Soremekun1Chisom Soremekun2Chisom Soremekun3Daudi Jjingo4Daudi Jjingo5Daudi Jjingo6David Kateete7Oyekanmi Nash8Dorothea Nitsch9Moffat Nyirenda10Moffat Nyirenda11Dipender Gill12Eleftheria Zeggini13Eleftheria Zeggini14Harald Grallert15Harald Grallert16Annette Peters17Annette Peters18Annette Peters19Tinashe Chikowore20Tinashe Chikowore21Chiara Batini22Chiara Batini23Opeyemi Soremekun24Opeyemi Soremekun25Segun Fatumo26Segun Fatumo27The African Computational Genomics (TACG) Research Group, MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, UgandaDepartment of Immunology and Molecular Biology, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, UgandaCentre for Genomics Research and Innovation, NABDA/FMST, Abuja, NigeriaHelmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Institute of Epidemiology, Neuherberg, GermanyAfrican Center of Excellence in Bioinformatics and Data-Intensive Sciences, Kampala, UgandaDepartment of Computer Science, Makerere University, Kampala, UgandaInfectious Diseases Institute, Kampala, UgandaDepartment of Immunology and Molecular Biology, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, UgandaCentre for Genomics Research and Innovation, NABDA/FMST, Abuja, NigeriaDepartment of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London School of Hygiene and Tropical Medicine, United KingdomDepartment of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London School of Hygiene and Tropical Medicine, United KingdomMRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Uganda0Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom1Institute of Translational Genomics, Helmholtz Zentrum München – German Research Center for Environmental Health, Neuherberg, Germany2TUM School of Medicine, Technical University of Munich and Klinikum Rechts der Isar, Munich, GermanyHelmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Institute of Epidemiology, Neuherberg, Germany3German Center for Diabetes Research (DZD), München-Neuherberg, Neuherberg, GermanyHelmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Institute of Epidemiology, Neuherberg, Germany3German Center for Diabetes Research (DZD), München-Neuherberg, Neuherberg, Germany4Chair of Epidemiology, Institute for Medical Information Processing, Biometry and Epidemiology, Medical Faculty, Ludwig-Maximilians-Universität München, Munich, Germany5Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School Boston, Boston, MA, United States6Wits Donald Gordon Medical Centre, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa7Department of Population Health Sciences, University of Leicester, Leicester, United Kingdom8University Hospitals of Leicester NHS Trust, Leicester, United Kingdom1Institute of Translational Genomics, Helmholtz Zentrum München – German Research Center for Environmental Health, Neuherberg, Germany9Molecular Bio-computation and Drug Design Laboratory, School of Health Sciences, University of KwaZulu-Natal, Durban, South AfricaThe African Computational Genomics (TACG) Research Group, MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Uganda0Precision Healthcare University Research Institute, Queen Mary University of London, United KingdomIntroductionObservational studies have identified associations between hematological traits and type-2 diabetes mellitus (T2D). However, it is difficult to infer causal effects due to the potential of confounding. Our study utilizes the Mendelian randomization (MR) approach to address the above limitation and investigate the causal effect of hematological traits such as white blood cell (WBC), platelets (PLT), and red blood cell (RBC) on T2D in individuals of African ancestry.MethodsThe participating cohorts included participants of African ancestry in the Blood Cell consortium and the Million Veteran Program dataset. Using GWAS summary statistics, we applied a univariable and multivariable Two-sample MR to estimate the causal relationship between hematological traits and T2D.ResultsIn the main IVW MR estimates, genetically predicted levels of mean corpuscular hemoglobin concentration (MCHC), mean corpuscular hemoglobin (MCH), and mean corpuscular volume (MCV) were associated with decreased risk of T2D. We also observed a decreased risk of T2D with genetically predicted total WBC count and neutrophil count (NEU), for the WBC traits. The multivariable analysis further supported the direct associations of genetically predicted MCH, MCHC, and MCV levels with a decreased risk of T2D. For the European ancestry, a similar pattern of association was observed for MCH and MCV.DiscussionThese findings indicate that hematological traits may differentially play a role in the development of T2D and be affected by T2D. However, further research is needed to validate and explore the biological pathways and mechanisms involved in these associations.https://www.frontiersin.org/articles/10.3389/fphar.2025.1436972/fullType-2 diabetesblood cell traitsmendelian randomizationAfricaHematological traits |
| spellingShingle | Chisom Soremekun Chisom Soremekun Chisom Soremekun Chisom Soremekun Daudi Jjingo Daudi Jjingo Daudi Jjingo David Kateete Oyekanmi Nash Dorothea Nitsch Moffat Nyirenda Moffat Nyirenda Dipender Gill Eleftheria Zeggini Eleftheria Zeggini Harald Grallert Harald Grallert Annette Peters Annette Peters Annette Peters Tinashe Chikowore Tinashe Chikowore Chiara Batini Chiara Batini Opeyemi Soremekun Opeyemi Soremekun Segun Fatumo Segun Fatumo Mendelian randomization study highlights the role of hematological traits on Type-2 diabetes mellitus in African ancestry individuals Frontiers in Pharmacology Type-2 diabetes blood cell traits mendelian randomization Africa Hematological traits |
| title | Mendelian randomization study highlights the role of hematological traits on Type-2 diabetes mellitus in African ancestry individuals |
| title_full | Mendelian randomization study highlights the role of hematological traits on Type-2 diabetes mellitus in African ancestry individuals |
| title_fullStr | Mendelian randomization study highlights the role of hematological traits on Type-2 diabetes mellitus in African ancestry individuals |
| title_full_unstemmed | Mendelian randomization study highlights the role of hematological traits on Type-2 diabetes mellitus in African ancestry individuals |
| title_short | Mendelian randomization study highlights the role of hematological traits on Type-2 diabetes mellitus in African ancestry individuals |
| title_sort | mendelian randomization study highlights the role of hematological traits on type 2 diabetes mellitus in african ancestry individuals |
| topic | Type-2 diabetes blood cell traits mendelian randomization Africa Hematological traits |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1436972/full |
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