Academic Journal
CRP-albumin-lymphocyte index and multisystem diseases: a phenome-wide Mendelian randomization study.
| Τίτλος: | CRP-albumin-lymphocyte index and multisystem diseases: a phenome-wide Mendelian randomization study. |
|---|---|
| Συγγραφείς: | Niu B; The Children's Hospital of Soochow University, School of Public Health, Suzhou Medical College of Soochow University, Suzhou, Jiangsu, P. R. China.; Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non-communicable Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology, Soochow University, Suzhou, Jiangsu, P. R. China., Xia MH; The Children's Hospital of Soochow University, School of Public Health, Suzhou Medical College of Soochow University, Suzhou, Jiangsu, P. R. China.; Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non-communicable Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology, Soochow University, Suzhou, Jiangsu, P. R. China., Wu JX; The Children's Hospital of Soochow University, School of Public Health, Suzhou Medical College of Soochow University, Suzhou, Jiangsu, P. R. China.; Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non-communicable Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology, Soochow University, Suzhou, Jiangsu, P. R. China., He P; The Children's Hospital of Soochow University, School of Public Health, Suzhou Medical College of Soochow University, Suzhou, Jiangsu, P. R. China.; Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non-communicable Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology, Soochow University, Suzhou, Jiangsu, P. R. China., Bo L; Department of Rheumatology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P. R. China., Wu HY; Department of Endocrinology and Genetic Metabolism, The Children's Hospital of Soochow University, Suzhou Medical College of Soochow University, Suzhou, Jiangsu, P. R. China., Lei SF; The Children's Hospital of Soochow University, School of Public Health, Suzhou Medical College of Soochow University, Suzhou, Jiangsu, P. R. China. leisf@suda.edu.cn.; Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non-communicable Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology, Soochow University, Suzhou, Jiangsu, P. R. China. leisf@suda.edu.cn.; Department of Endocrinology and Genetic Metabolism, The Children's Hospital of Soochow University, Suzhou Medical College of Soochow University, Suzhou, Jiangsu, P. R. China. leisf@suda.edu.cn., Deng FY; The Children's Hospital of Soochow University, School of Public Health, Suzhou Medical College of Soochow University, Suzhou, Jiangsu, P. R. China. fdeng@suda.edu.cn.; Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non-communicable Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology, Soochow University, Suzhou, Jiangsu, P. R. China. fdeng@suda.edu.cn.; School of Public Health, Suzhou Medical College of Soochow University, Suzhou, 215123, P.R.China, P.R. of China. fdeng@suda.edu.cn. |
| Πηγή: | Molecular genetics and genomics : MGG [Mol Genet Genomics] 2026 Sep 28; Vol. 301 (1). Date of Electronic Publication: 2026 Sep 28. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Springer-Verlag Country of Publication: Germany NLM ID: 101093320 Publication Model: Electronic Cited Medium: Internet ISSN: 1617-4623 (Electronic) Linking ISSN: 16174623 NLM ISO Abbreviation: Mol Genet Genomics Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Berlin : Springer-Verlag, c2001- |
| Ιατρικοί όροι (MeSH): | Mendelian Randomization Analysis*/methods , C-Reactive Protein*/metabolism , C-Reactive Protein*/genetics , Lymphocytes*/metabolism, Genome-Wide Association Study/methods ; Phenomics/methods ; Inflammation/genetics ; Humans ; Polymorphism, Single Nucleotide ; Biomarkers ; Phenotype ; Genetic Predisposition to Disease |
| Περίληψη: | The C-reactive protein-albumin-lymphocyte (CALLY) index is a composite biomarker integrating inflammation, nutrition, and immune function, but its causal relationships with a broad spectrum of human diseases and potential utility for public health risk prediction remain unclear. We conducted a population-based genetic epidemiological study combining genome-wide association study (GWAS), phenome-wide association study (PheWAS), and two-sample Mendelian randomization (MR), using data from the UK Biobank (265,409 participants for GWAS; 113,747 participants for PheWAS) and FinnGen to construct genetic instruments for the CALLY index, perform PheWAS across 713 phenotypes, evaluate causal associations via two-sample MR, and conduct sensitivity analyses including linkage disequilibrium score regression and pleiotropy testing. GWAS identified 154 genomic loci significantly associated with the CALLY index; PheWAS detected 24 significant phenotype associations, with higher genetically predicted CALLY index linked to lower risks of Alzheimer's disease, Alzheimer's dementia, unspecified dementia, and lipid metabolism disorders. MR confirmed causal protective effects for these neurodegenerative outcomes while indicating a causal association with increased sleep disorder risk, and pleiotropic analyses highlighted shared biological pathways in lipid metabolism and inflammation. These findings demonstrate that the CALLY index is causally associated with neurodegenerative, metabolic, and sleep disorders, supporting its role as a promising integrated biomarker for disease risk stratification and public health applications. (© 2026. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.) |
| Competing Interests: | Declarations. Conflict of interest: The author declares no conflicts of interest. Ethical approval: The Northwest Multi-center Research Ethics Committee (MREC reference: 21/NW/0157) provided ethical approval for the UK Biobank project. Consent to participate: All participants gave informed consent before being recruited (Application number 76875). |
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| Grant Information: | 82373587, 82173529, 82173598, and 82103922 Natural Science Foundation of China |
| Contributed Indexing: | Keywords: CALLY index; Chronic inflammation; Mendelian randomization; PheWAS; Public health |
| Substance Nomenclature: | 9007-41-4 (C-Reactive Protein) 0 (Biomarkers) |
| Entry Date(s): | Date Created: 20260928 Date Completed: 20260928 Latest Revision: 20261008 |
| Update Code: | 20261008 |
| DOI: | 10.1007/s00438-026-02513-0 |
| PMID: | 42803832 |
| Βάση Δεδομένων: | MEDLINE |
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