Causal association between blood leukocyte counts and vascular dementia: a two-sample bidirectional Mendelian randomization study

• Published in: Scientific reports Vol. 14; no. 1; pp. 19582 - 11
• Main Authors: Liu, Shufang, Zhang, Chenwei, Zhang, Yukai, Wu, Zhifang, Wu, Ping, Tian, Shouyuan, Zhang, Min, Lang, Limin, Li, Li, Wang, Ruonan, Liu, Haizhao, Zhang, Jingfen, Mao, Xiaolu, Li, Sijin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23.08.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/208; 631/378; 692/499; 692/617; Biobanks; Blood; Cell activation; Consortia; Dementia; Dementia disorders; Dementia, Vascular - blood; Dementia, Vascular - genetics; Female; Genome-wide association studies; Genome-Wide Association Study; Humanities and Social Sciences; Humans; Immune response; Leukocyte; Leukocyte Count; Leukocytes; Lymphocyte; Lymphocytes; Male; Mendelian randomization; Mendelian Randomization Analysis; multidisciplinary; Observational studies; Pathogenesis; Pleiotropy; Polymorphism, Single Nucleotide; Risk Factors; Science; Science (multidisciplinary); Sensitivity analysis; Sexually transmitted diseases; Statistical analysis; STD; Vascular dementia; United Kingdom > UK; Vascular dementia; Mendelian randomization; Leukocyte; Lymphocyte
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-70446-y

While previous observational studies have suggested a link between leukocyte counts and vascular dementia (VD), the causal relationship between leukocyte counts and various subtypes of VD remains elusive. This study aimed to investigate the causal relationship between five types of leukocyte counts and VD, with the goal of improving prevention and treatment strategies. In this study, leukocyte counts were used as the exposure variable, with genome-wide association study (GWAS) data sourced from both the UK Biobank and the Blood Cell Consortium. Additionally, GWAS data for five subtypes of vascular dementia were obtained from the FinnGen database. We conducted rigorous statistical analysis and visualization using Mendelian randomization (MR) to elucidate the potential causal relationship between leukocyte counts and vascular dementia. This study, utilizing MR analysis with data from the UK Biobank and Blood Cell Consortium, identified significant causal associations between increased lymphocyte counts and VD. Specifically, lymphocyte counts were found to be causally related to multiple and mixed VD subtypes. Sensitivity analyses, including MR-Egger regression and MR-PRESSO tests, confirmed the robustness of these findings, with no evidence of reverse causality or significant horizontal pleiotropy detected. The results underscore a potential inflammatory or immunological mechanism in the pathogenesis of VD, highlighting lymphocytes as a key component in their etiology. This investigation establishes a robust association between elevated lymphocyte and leukocyte counts and an increased risk of VD, emphasizing the roles of inflammation, immune activation, and hematological factors in disease pathogenesis.